Fucose in N-Glycans - From Plant To Man

Biochimica et Biophysica Acta 1473 (1999) 216^236
www.elsevier.com/locate/bba
Review
Fucose in N-glycans: from plant to man

Erika Staudacher *, Friedrich Altmann, Iain B.H. Wilson, Leopold Marz
Institut fur Chemie, Universitat fur Bodenkultur, Muthgasse 18, A-1190 Vienna, Austria
Received 3 February 1999; received in revised form 6 May 1999; accepted 27 May 1999
Abstract
Fucosylated oligosaccharides occur throughout nature and many of them play a variety of roles in biology, especially in a
number of recognition processes. As reviewed here, much of the recent emphasis in the study of the oligosaccharides in
mammals has been on their potential medical importance, particularly in inflammation and cancer. Indeed, changes in
fucosylation patterns due to different levels of expression of various fucosyltransferases can be used for diagnoses of some
diseases and monitoring the success of therapies. In contrast, there are generally at present only limited data on fucosylation
in non-mammalian organisms. Here, the state of current knowledge on the fucosylation abilities of plants, insects, snails,
lower eukaryotes and prokaryotes will be summarised. 1999 Elsevier Science B.V. All rights reserved.
Keywords: Fucosyltransferase; Fucose; Fucosylation; N-glycan; Glycobiology
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
217
2. Fucosylation of N-glycans in mammals . . . . . . . .

2.1. Fertilisation and development . . . . . . . . . . . .
2.2. Cell adhesion mediated by selectins . . . . . . . .
2.3. Fucosylation in cancer . . . . . . . . . . . . . . . . .
2.4. Other fucosylation events related with disease
2.5. Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
217
218
218
219
219
219
3. Mammalian Fuc-Ts . . . . . . . . . . . . . . . .
3.1. Human K1,2-Fuc-Ts . . . . . . . . . . . .
3.2. Human K1,3/4-Fuc-Ts . . . . . . . . . . .
3.3. Terminal Fuc-Ts of other mammals .
3.4. K1,6-Fucosylation . . . . . . . . . . . . . .
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
220
220
220
220
221
4. Insects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
222
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Abbreviations: Fuc, fucose; Gal, galactose ; GalNAc, N-acetylgalactosamine; GlcNAc, N-acetylglucosamine; Man, mannose; Xyl,
xylose; Fuc-T, fucosyltransferase
* Corresponding author. Fax: +43 (1) 36006-6059; E-mail: estaud@edv2.boku.ac.at
0304-4165 / 99 / $ ^ see front matter 1999 Elsevier Science B.V. All rights reserved.
PII: S 0 3 0 4 - 4 1 6 5 ( 9 9 ) 0 0 1 8 1 - 6
BBAGEN 24929 17-11-99
E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236
217
5. Snails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
222
6. Trematodes and nematodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
223
7. Amoeba . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
224
8. Fucosylation in other animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
224
9. Prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
224
10. Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
225
11. Relationships of Fuc-Ts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
225
12. Fucosylation and biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
225
13. Future aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
226
14. Note added in proof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
226
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
226
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
226
1. Introduction
The basic biosynthetic pathway of N-glycans in
eukaryotes is a highly conserved process [1,2], but
the microheterogeneity of the glycans depends on
the organism, the tissue and the developmental and
physiological status of the cell by the availability of
processing glycosidases and glycosyltransferases as
well as accessibility of the glycans [3]. The improvement in methods for glycan analysis [4] and in molecular biology has caused an immense increase in
the amount of knowledge about glycans involved in
various recognition processes and on the corresponding glycosyltransferases. One feature that often varies
is the number and the type of linkage of fucose (Fuc)
residues. Normally, in N-glycans, Fuc is attached in
K-linkage to galactose (Gal) in 1,2 or to N-acetylglucosamine (GlcNAc) residues in 1,3, 1,4 or 1,6. Direct
fucosylation of peptides, which is also known, has
been reviewed elsewhere [5]. The correlation of
fucosylation patterns with adhesion events and various diseases led to intensive investigations on,
especially human, fucosyltransferases (Fuc-Ts) and
their regulation during developmental or pathological processes. Once the human Fuc-T genes were
analysed, sequences from other sources could be
identied. Now, more than 150 entries of complete

or partial sequences of Fuc-Ts from prokaryotic
as well as eukaryotic origin can be found through
the internet (e.g. NCBI GenBank: 6 http://
www.ncbi.nlm.nih.gov/Entrez/index.html s or ExPASy, Swiss-Prot: 6 http://www.expasy.ch/cgi-bin/
sprot-search-ful s ). Since the number of entries is
rapidly increasing, a printed list would go out of
date quickly and is therefore omitted here.
Normally, research on non-mammalian organisms
is only carried out if these organisms are of some
medical or commercial interest. Therefore, some
data exist on human pathogens, venoms and plant
pollen or food allergens. Furthermore, plant and insect cells which are potential, or already used, expression systems for the production of recombinant (glyco)proteins have been studied for their glycosylation
abilities. Although a summary of recent literature on
fucosylation in eukaryotes generally is given here, we
place particular emphasis on non-mammalian systems.
2. Fucosylation of N-glycans in mammals
In mammalian tissues, Fuc can be linked K1,2 to
BBAGEN 24929 17-11-99
218
ing, until adult patterns appeared, inuenced also by

the manipulation of nutritional factors [16^20].
Changes in fucosylation activity occur not only in
the young animal but also in the pregnant mother.
The degree of branching and K1,6-fucosylation is increased on human glycoprotein hormone K-subunit
glycans during the second trimester of pregnancy
[21].
2.2. Cell adhesion mediated by selectins
Fig. 1. Typical mammalian complex N-glycans.
terminal Gals, K1,3 or K1,4 to subterminal GlcNAc

residues of the antennae and K1,6 to the innermost
GlcNAc (Fig. 1). Various functions have been, and
will be, found for Fuc residues, especially those decorating the outer chains of oligosaccharides. They
play an important role in several cell recognition
processes ranging from fertilisation and development
through to pathological events and cell death.
2.1. Fertilisation and development
Protein-carbohydrate interactions regulate, at least
in part, the binding of the sperm to the zona pellucida [6]. For example, in porcine zona pellucida, a
number of negative-charged, fucosylated N-glycans
have been found to be involved in sperm binding
[7^9]. In the bovine and murine systems, the requirement of a Fuc residue is possible [10,11]. However,
whereas the tetrasaccharide epitope FucK1,2GalL1,3(FucK1,4)GlcNAc- is present in N- and Oglycans of the human zona pellucida, this structure
was not detected on bovine or porcine oligosaccharides [12]. This leads to the hypothesis that speciesspecic glycosylation regulates sperm binding. This
theory is supported by the fact that human oocytes
that cannot be fertilised in vitro display a slightly
altered carbohydrate distribution [13]. In addition,
Fuc-Ts and their products were identied on rat epididymal spermatozoa where they may also be involved in adhesion processes [14,15].
In the course of development, changes in fucosylation activities can be observed in the various tissues
of young animals. A number of changes in fucosylation patterns were found in rats from the day of
birth, during the suckling period, shortly after wean-
There are much data to indicate that K1,3-fucosylated carbohydrates (for abbreviations, see Table
1) and their sulfated and sialylated variants act as
ligands for selectins, a family of adhesion receptors.
L-selectin (LAM-1, LECAM-1) is a constitutively expressed lymphocyte homing receptor of most leukocytes, while E-selectin (ELAM-1, LECAM-2) is expressed on the cell surface of endothelial cells after
activation with cytokines and endotoxins and P-selectin (GMP-140, PADGEM, LECAM-3) is a rapidly inducable receptor expressed on the plasma
membrane of endothelial cells and platelets [22^24].
The carbohydrate recognition process is involved in
several acute and chronical inammatory disorders
such as rheumatoid arthritis and skin inammation.
These medical aspects encouraged basic research in
Table 1
Names and structures of acceptors and products of Fuc-Ts
BBAGEN 24929 17-11-99
this area. The great number of resulting publications

can be divided into three groups. (i) Carbohydrate
analysis: elucidation of the preferred ligands of the
selectins and the characteristic ligand patterns of specic types of cells, e.g. [25^27]. (ii) Identication of
the Fuc-T(s) which are responsible for forming the
typical ligands, in particular the roles of Fuc-T VI
and Fuc-T VII are under continuing investigation,
e.g. [28^35]. (iii) Attempts to reduce or to inhibit
the binding by modication of the carbohydrate ligand or by the construction of inhibitors, e.g. [36^
42]. These results could lead to the development of
anti-adhesion therapeutics in the near future.
2.3. Fucosylation in cancer
Protein-linked glycans in cancer cells are generally
highly branched and often, their oligosaccharide
composition is altered compared with normal cells.
The presence of such tumour-associated carbohydrates can give information on the potential malignity of a tumour and its metastasising potential. In
addition, such correlations are helpful in the diagnosis, are of prognostic value and aid the observation
of the progress of therapy [43]. The glycans are involved in the immunological response of the organism, cell adhesion during metastasis and modulation
of the function of proteins [44]. Often, the number
and type of linkage of Fuc and sialic acid residues
are characteristic for several tumours. In parallel
with an increased number of fucosylated glycans,
the expression of the corresponding Fuc-Ts is also
elevated.
In lung carcinoma, the enhanced expression of
Fuc-T IV and VII is related to a high metastatic
potential and a poor prognosis [45^47], while increased synthesis of sialyl Lex structures by Fuc-T
III is involved in colon cancer metastasis [48,49].
Patients who express these structures have a signicantly poorer disease-free survival rate [50]. Dierent
reports suggest increased Fuc-T III or Fuc-T V activities in human intestinal cancers [51^53].
The role of the enzymes responsible for the accumulation of K1,2-fucosylated antigens is a matter of
controversy. While transfection of poorly tumourogenic rat colon carcinoma cells with human H-type
K1,2-Fuc-T enabled these cells to form progressive
tumours [54], in human colon adenocarcinoma cell
219
lines, only Se-type K1,2-Fuc-T was expressed [55]. In

addition, a new K1,2-Fuc-T activity associated with
Fuc-T III and exhibiting dierent substrate-specicities was identied in colon carcinoma cells [56,57].
In hepatocarcinogenesis, the increased level of
K1,6-Fuc-T expression and its products correlate in
humans and rats with tumour development [58,59].
However, in chronic hepatitis and liver cirrhosis,
K1,6-Fuc-T activity was found also to be increased
compared with normal liver [60^62]. In patients with
neoplastic diseases of the liver, not only fucosylation
but also the degree of branching of the N-glycans of
K-fetoprotein has to be taken into account to provide
an accurate criterion for tumour identication
[63,64].
Also several other types of carcinomas were found
to exhibit increased fucosylation of surface glycans
involved in selectin-mediated binding and enhanced
expression of Fuc-Ts. However, the exact mechanism
of this up-regulation and the identity of the relevant
enzymes is still not clear, antibodies against these
overexpressed epitopes coupled with cytotoxic agents
are considered as anti-cancer vaccines [65].
2.4. Other fucosylation events related with disease
There are a number of recently published reviews
in which glycosylation in disease is discussed [66^68].
Since Fuc is a relevant part of several ligands involved in adhesion processes (see above), it is not
really surprising that additional pathological recognition events, invasion of viruses, bacteria or parasites are dependent on fucosylated glycans [69].
While it is possible in the future that genetic therapy will enable the correction of defects in the expression of Fuc-Ts, lysosomal fucosidases and synthesis of GDP-Fuc, pathological processes where Fuc
is part of an epitope in an adhesion process may be
inuenced by well-designed and optimally targeted
drugs.
2.5. Apoptosis
Fucosylation also seems to play a role during the
programmed cell death, apoptosis. Mouse thymocytes and P815 cells showed an increased amount
of exposed Fuc residues on the cell surface after induction of apoptosis by three dierent agents, dexa-
BBAGEN 24929 17-11-99
220
methasone, gliotoxin and thapsigargin [70]. Histological studies of many tumours and normal tissues revealed close correlation of elevated Ley expression
with the process of apoptosis [71]. In human HAT29 colon adenocarcinoma cells, strongly enhanced
expression of Lex and slightly enhanced expression
of Ley were observed on the cell surface prior to
cell death. The Lex expression correlated with an
increased activity of K1,3-Fuc-T IV [72]. Due to the
fact that increased fucosylation was observed in different cell types after induction of apoptosis by different agents, it seems to be not a signal but one of
the results of the `program' for cell death.
3. Mammalian Fuc-Ts
3.1. Human K1,2-Fuc-Ts
K1,2-Fuc-Ts catalyse the transfer of a Fuc residue
into K1,2-linkage to a terminal Gal residue of N- or
O-glycans, a necessary step in the formation of ABO
blood group antigens [73]. An additional Fuc K1,3or K1,4-linked to the penultimate GlcNAc or sialic
acid K2,3- or K2,6-linked to the Gal normally blocks
the transfer. In human tissues, two enzymes sharing
this specicity have been found (reviewed in [74]).
The H-type enzyme is found in haematopoietic cells
and plasma and prefers type 2 acceptor substrates.
However, it fucosylates also phenyl-L-D-galactosides.
The Se-type enzyme occurs in secretory uids and
tissues of ABO blood group secretors and prefers
both type 1 and type 3 acceptors [75]. Both enzymes
have been cloned [76,77] and their genes (FUT1 and
FUT2, respectively) were found to be located close to
each other on human chromosome 19.
Individuals with mutations in one of the two genes
fail to express or have reduced expression of A, B
and H antigens on the surface of dierent tissues (Hand Se-enzyme are decient in variants of the socalled Bombay phenotype) [78^81]. These phenotypes have a relatively high frequency in some populations and apparently do not exhibit any harmful
eects. Therefore, they can be used for inheritance
studies.
A third type of K1,2-Fuc-T associated with the
K1,4 activity was found in several human carcinoma
tissues and co-puried with K1,4-Fuc-T from colon
carcinoma Colo 205 cells. The enzyme reveals a

broad specicity combined with a high eciency
and may be potentially involved in malignancy [56].
3.2. Human K1,3/4-Fuc-Ts
Five human K1,3-Fuc-Ts (Fuc-T III^VII) have
been cloned [82^90] and are a family of closely related membrane bound glycosyltransferases. Their
genes (FUT3^7) are highly homologous. Three of
them (FUT3, FUT5 and FUT6) are located very close
to each other in a cluster on chromosome 19p13.3
[91]. They are distinguishable by acceptor specicity
and biochemical as well as kinetic parameters. Their
expression depends on the tissue and the developmental and physiological status of the cell. Fuc-T
III is noteworthy one of the rarely occurring glycosyltransferases that catalyse the formation of two
dierent glycosidic linkages, since it acts as both an
K1,3- and an K1,4-Fuc-T depending on the substrate.
Details on all of these enzymes can be found in a
number of reviews which have been published in recent years [92^95].
In human tissues, normally, a mixture of several
activities is responsible for the observed fucosylation.
With genetic methods, individual recombinant enzymes were characterised in various systems, free
from interfering activities [96^103]. The identication
of these genes and modern methods of molecular
biology make it possible to evaluate the distribution
of single enzymes in various tissues or to study their
contribution to developmental processes [104^108].
Furthermore, site-directed mutagenesis of these enzymes has been performed to ascertain the roles of
certain amino acid residues in binding of GDP-Fuc,
acceptor specicity, kinetic parameters or inhibitor
sensitivity [109^118]. Such results may allow for the
future development of genetic therapies for patients
with defects in their fucosylation potentials. Today,
the information can help to optimise Fuc-Ts for the
production and modication of oligosaccharides necessary in research or therapy.
3.3. Terminal Fuc-Ts of other mammals
Recently, a number of Fuc-T genes from other
mammals have been cloned by homology to the human Fuc-Ts. This reveals information on the evolu-
BBAGEN 24929 17-11-99
tion of these enzymes. For instance, the chimpanzee

possesses FUT3, FUT5 and FUT6 genes with about
98% sequence homology to the corresponding human
genes [119]. In contrast, there is a single bovine gene,
corresponding to the human gene cluster FUT3FUT5-FUT6, whose gene product shares more than
60% amino acid sequence identity with all three of
the human enzymes [120].
In rodents, a Fuc-T IV has been cloned from mice
[121,122] and rat [123] while Fuc-T VII has only been
cloned from mice [124]. Furthermore, a novel murine
K1,3-Fuc-T (mFuc-T IX) was cloned and its transcripts were detected in mouse brain, kidney and
neuronal cells. The enzyme shows below 50% homology to all other known Fuc-Ts, thus it does not
belong to any subfamily of the known K1,3-Fuc-Ts.
The substrate specicity of mouse Fuc-T IX is similar to human Fuc-T IV and forms Lex epitopes, but
not sialylated Lex structures. The enzyme is considered to participate in the Lex synthesis in neurons of
the brain [125]. Also in some rat cells, an K1,4-Fuc-T
activity has been detected [126,127], thus at least one
additional enzyme with some similarities to Fuc-T III
awaits cloning of its gene.
Chinese hamster ovary (CHO) cells, a frequently
used expression system for glycosyltransferases, were
initially thought not to express any K1,3-Fuc-T activity. However, following mutagenesis or transfection with large amounts of foreign DNA, mutants
that express K1,3-Fuc-T activity have been obtained
[128,129]. Also after the transfection of a human
K1,3-Fuc-T gene, false positive clones from the activation of an endogenous enzyme complicated the
identication of the transfectants [130]. Thus, CHO
cells contain Fuc-T gene(s) that are normally quiescent, but can be activated by mutational events. In
another frequently used cell line, monkey kidney
COS-7 cells, three dierent endogenous Fuc-Ts
were identied, one revealing a similar acceptor specicity as Fuc-T IV [131].
Rabbits contain three dierent active K1,2-Fuc-Ts.
One of them (RFT-I) shows more than 80% identity
with the human H-type enzyme. Both other enzymes
(RFT-II, RFT-III) are highly homologous to each
other. Their acceptor specicity, preference of type
1 and type 3 acceptors, suggests that they are putative Se-type enzymes [132,133]. All rabbit Fuc-Ts are
developmentally regulated [134].
221
Rats and mice contain both analogues to human

K1,2-Fuc-Ts [135,136]. From pigs, a H-type K1,2Fuc-T has been cloned [137] and a partial amino
acid sequence of a porcine Se-type homologous enzyme was determined from submaxillary gland [138].
3.4. K1,6-Fucosylation
Fuc in K1,6-linkage to the asparagine-linked
GlcNAc residue of a N-glycan is a typical mammalian feature [139]. In vivo, K1,6-fucosylation protects
glycans in humans against hydrolysis by glycoasparaginase [140] and is one necessary requirement for
polysialylation [141]. However, K1,6-fucosylation of
the innermost GlcNAc residue has also been found
in insects and snails (see later), but so far never in
plants. This type of enzyme was rst extensively
characterised, around 20 years ago, in Harry Schachter's laboratory from rat and porcine liver microsomes [142,143]. About 10 years later, the rst purication, from cultured human skin broblasts, was
reported [144]. More recently, the enzyme was cloned
from porcine brain [145] and a human gastric cancer
cell line (MKN45) [146]. A puried K1,6-Fuc-T from
human platelets shares acceptor specicity and biochemical parameters, such as a lack of necessity for
cations, with the cloned ones [147].
All these K1,6-Fuc-T activities require an unsubstituted GlcNAc residue in the C2 position to the
mannose (Man) of the K1,3-antennae of the N-glycan
for the transfer. However, the presence of K1,6-Fuc
on structures lacking the GlcNAc on the K1,3-branch
has been reported in some cases [148^151]. This may
either be due to alternative Fuc-T activities, a residual activity of Fuc-T towards structures lacking the
non-reducing terminal GlcNAc, or, akin to the case
in plants and insects, a processing L-hexosaminidase
[152,153].
A bisecting GlcNAc residue, linked L1,4 to the LMan of the core [154], or the prior addition of an
K1,3-linked Fuc to the innermost GlcNAc are
`NOGO' signals for transfer [155]. Furthermore, the
enzyme is not able to catalyse a linkage if a chemical
alteration of the GlcNAc occurred, for example by
uorescent labelling. Therefore, new methods had to
be developed to show a specic incorporation in vitro [156,157].
BBAGEN 24929 17-11-99
222
Fuc-T is inhibited by prior K1,3-fucosylation of the

inner GlcNAc, thus, in biosynthesis of difucosylated
glycans, the K1,6-Fuc-T must act before the K1,3Fuc-T [155]. For further details on insect glycosylation and their use as hosts for the expression of recombinant glycoproteins, the reader is referred to
other reviews from this laboratory [171^174].
5. Snails
Fig. 2. Fucosylated insect N-glycans.
4. Insects
Structural analysis of insect N-glycans reveals that
they can be fucosylated in three possible ways (Fig.
2). (i) Fucosylation in K1,6-linkage to the innermost
GlcNAc as found in mammals, (ii) in K1,3-linkage
again to the proximal GlcNAc residue as in plants
and (iii) the formation of N-acetylgalactosamine
(GalNAc)L1,4(FucK1,3)GlcNAcL1,2 (K1,3-fucosylated LacdiNAc). A selection of N-glycans from honeybee (Apis mellifera) venom phospholipase A2
shows all three of these modications [158]. The rst
core-difucosylated N-glycan to be described was
from this source [159]. Subsequently, such difucosylation was also found in other honeybee venom glycoproteins [160], lepidopteran cells [161], on oligosaccharides of a trematode [162] and a nematode [163].
Apart from honeybee (A. mellifera) venom glycoproteins [158,160], the K1,3-fucosylated `LacdiNAc'
structure has only been found rarely in other organisms: in bovine pro-opiomelanocortin [164], human
urokinase [165], recombinant human protein C expressed in human kidney cells [166], a schistosome
[167] and a pit viper [168].
While no information exists on the transferase responsible for fucosylating the terminal antennae, the
fucosylation activities required for both types of insect core fucosylation are characterised in terms of
their acceptor specicity. Both, the K1,6- and the
K1,3-Fuc-Ts require an unsubstituted GlcNAc residue linked to the K1,3-antennae, similar to the substrate requirements of mammalian K1,6-Fuc-Ts (see
above) [169]. The biosynthesis of core-difucosylated
glycans proceeds in a strict order: the K1,3-Fuc-T is
able to convert non-fucosylated as well as K1,6-fucosylated acceptor substrates [170]. However, the K1,6-
The rst analysis of a snail N-glycan was carried

out on Helix pomatia K-hemocyanin by van Kuik et
al. in 1985 (Fig. 3a) [175]. The major low molecular
weight N-glycan of this protein was found to be a
Man3 GlcNAc2 -core with a Fuc K1,6-linked to the
inner GlcNAc and a L1,2-linked xylose (Xyl) attached to the L-Man residue. It was the rst time
that Xyl was found as a component of an animal
N-glycan. Further studies on the K-hemocyanins of
H. pomatia and Lymnea stagnalis conrmed L1,2linked Xyl as a typical component of snail N-glycans.
While fucosylation in H. pomatia is restricted to an
K1,6-Fuc to the inner core, L. stagnalis exhibits K1,2linked Fucs to terminal Gal residues (Fig. 3b)
[176,177]. The K1,2-Fuc-T responsible for these units
prefers GalL1,3GalNAc over type 1 or type 2 acceptors and is therefore dierent from other K1,2-FucTs described. Furthermore, in connective tissue as
well as albumen glands of L. stagnalis, an K1,3Fuc-T activity was found which utilises type 2 acceptors to form Lex structures [178]. However, no
Fig. 3. Fucosylated N-glycans from snails. (a) H. pomatia [175],

(b) L. stagnalis [176].
BBAGEN 24929 17-11-99
223
corresponding K1,3-fucosylated glycans have been

detected so far. Preliminary data from our own laboratory on Arionta species would suggest that a
broader, non-protein-specic approach for the investigation of the snail `glycome' will lead to the discovery of unexpected, perhaps so far unknown structures.
6. Trematodes and nematodes
During the past years, the investigation of helminth glycosylation revealed several remarkable
new structures presumably playing a role in host^
parasite interactions. They may be promising targets
which can be used for vaccine development.
For example, blood ukes of the genus Schistosoma are helminthic parasites causing schistosomiasis,
a vascular parasitic disease aicting millions of people world-wide. This parasite has a complex life cycle
involving an invertebrate (fresh water snail) and a
vertebrate host. A developmentally regulated expression of Lex antigens was detected in O- and N-glycans of adult worms, these glycans induce changes in
immune cell populations and the production of cytolytic autoantibodies in the vertebrate hosts
[167,179,180]. The corresponding K1,3-Fuc-T has
an acceptor specicity and biochemical properties resembling those of human Fuc-T IV [181]. In addition
to terminal Lex determinants, the glycoproteins of
Schistosoma mansoni and Schistosoma japonicum
eggs contain K1,3- and K1,6-core-fucosylated as
well as K1,3/K1,6-difucosylated N-glycans with or
without a L1,2-linked Xyl residue (Fig. 4a) [162].
Thus far, this is the only example of K1,3/K1,6-difucosylated N-glycans carrying Xyl residues.
The cercariae of the avian schistosome Trichobilharzia ocellata contain an K1,2- and an K1,3-Fuc-T
involved in the biosynthesis of the FucK1,2FucK1,3GlcNAc element occurring on the O-glycans
and glycosphingolipids of this organism [182^184].
The acceptor specicity of the K1,3-Fuc-T resembled
in vitro human Fuc-Ts V and VI, showing a preference for structures based on type 2 chains, whereas
type 1 chains were only poor acceptors. The K1,2Fuc-T described is the rst Fuc-T identied transferring Fuc from GDP-Fuc to another Fuc residue
Fig. 4. Fucosylated N-glycans of helminths. (a) S. mansoni

[162], (b) H. contortus [163].
forming the unit FucK1,2Fuc. Therefore, no comparison with other K1,2-Fuc-Ts is possible.
None of the nematodes (Dirolaria immitis, Haemonchus contortus, Caenorhabditis elegans) or other
trematodes (Fasciola hepatica) investigated were
found to express glycans containing Lex or sialylated
Lex determinants, but several of the glycoproteins
bound to Lotus tetragonolobus agglutinin, which is
specic for FucK1,3GlcNAc structures [185].
Although C. elegans and H. contortus apparently
do not express Lex antigens, K1,3-Fuc-Ts capable of
this type of fucosylation have been identied in their
extracts and were cloned [186,187]. The C. elegans
enzyme (CEFT-1) expressed in COS-7 cells synthesised Lex but not sialylated Lex units. Besides the
cloned enzyme, another K1,3-Fuc-T activity, which
could also fucosylate sialylated acceptors, and an
K1,2-Fuc-T activity specic for type 1 chains were
detected [186]. The H. contortus enzyme has properties which resemble those of the cloned C. elegans
enzyme except that it also can utilise sialylated acceptors [187]. However, due to the lack of a L1,4galactosyltransferase, the biological function of these
enzymes is hypothesised to be in the synthesis of
terminal FucK1,3GlcNAc- and K1,3-fucosylated LacdiNAc structures.
Furthermore, a unique type of fucosylation has
been found in H. contortus: three Fucs are attached
to the inner core of the N-glycan. Two in K1,3 and
K1,6 position of the proximal GlcNAc, the third one
in K1,3 position of the distal GlcNAc of the chitobiose unit (Fig. 4b) [163].
BBAGEN 24929 17-11-99
224
7. Amoeba
In the slime mold Dictyostelium discoideum, a haploid amoeba, multiple types of fucosylation occur.
Fucosylation has been shown to be essential for the
formation and proteolytic protection of spores and
for their eective germination. Using specic antibodies, Fuc and phosphoFuc O-linked to serine
and K1,3- as well as K1,6-core-fucosylated N-glycans
were detected [188^190]. The Fuc-Ts acting on the Nglycans are developmentally regulated. Core K1,3Fuc-T activity was exclusively found during development, whereas K1,6-Fuc-T activity reached its maximum during growth and decreased during development [190].
Furthermore, an K1,2-Fuc-T activity utilising type
1 oligosaccharides in vitro was found in the cytosol
of D. discoideum [191,192]. The substrate specicity
of this enzyme resembles the human Se-type K1,2Fuc-T but its acceptors in vivo are the Xyl and
Gal containing O-glycans of a highly conserved fucoprotein (FP21). The fucosylation of this protein
occurs in the cytosol, which explains the unusual
location and the absence of a transmembrane domain in the Fuc-T [193].
8. Fucosylation in other animals
So far, the only bird where fucosylation has been
investigated is chicken. An K1,3-Fuc-T related to human Fuc-T IV with about 50% homology to the
human and mouse enzymes was cloned and characterised [194] and organ-specic distribution of K1,6fucosylation of transferrin was detected [195].
N-glycans puried from the ovarian uid of rainbow trout contain K1,6-linked Fuc linked to the inner core as well as polysialic acid-modied Lex determinants on the antennae [196]. Recently, two new
K1,3-Fuc-T genes have been detected in the zebrash
genome. They synthesise Lex structures, but although
they show signicant homology in general to other
K1,3-Fuc-Ts, they are not specically related to any
single one (S. Natsuka, N. Kageyama, S. Hase, Int.
Carbohydrate Symposium 1998, San Diego, CA,
USA).
A non-terminal Fuc occurring in the novel
GalL1,4Fuc unit linked K1,6 to the inner GlcNAc
Fig. 5. N-glycan from octopus rhodopsin [197].
was found on a N-glycan from octopus rhodopsin

(Fig. 5) [197]. However, this is the only example
for such a structure. In general, there are little data
on invertebrate glycoproteins, thus it remains possible that this structure will be found elsewhere. In
amphibians, highly fucosylated O-glycans are usual,
which contain various non-terminal Fucs. There,
they are perhaps involved in the fertilisation process
and may be a valuable model to examine changes in
O-linked carbohydrate structures during evolution
[198].
The venom of the funnel web spider (Agelenopsis
aperta) contains K1,6-fucosylated N-glycans [151]
and the venom of a pit viper (Bothrops moojeni) contains glycoproteins carrying a Fuc linked K1,6 to the
core and an K1,3-linked Fuc attached to GlcNAc
residues of the antennae [168].
9. Prokaryotes
The rst, and so far the only, prokaryote revealing
a fucosylated oligosaccharide related to those of
higher organisms is Helicobacter pylori. It is a human
pathogenic Gram-negative bacterium causing gastritis, gastric and duodenal ulcer and gastric adenocarcinoma. It may colonise the human gastric mucosa
by adhesion to Leb antigens of gastric epithelial cells
[199]. Fucosylated antigens play an important role in
the course of its infection. The Lex and Ley determinants expressed on lipopolysaccharides of the microorganism mimic human cell surface glycoconjugates
and induce autoantibodies, which may result in the
changes revealed in the gastric mucosa by immunohistopathology [200,201]. Cloning of the H. pylori
K1,3-Fuc-T responsible for forming the Lex determinant and comparing it with mammalian K1,3-Fuc-Ts
revealed only a short highly conserved region. Fur-
BBAGEN 24929 17-11-99
thermore, the enzyme lacks the transmembrane region typical for eukaryotic Fuc-Ts [202,203].
A novel Fuc-T activity was found in various soil
bacteria (Bradyrhizobium japonicum, Azorhizobium
caulinodans, Rhizobium loti). This bacterial nodulation protein (NodZ) fucosylates in vivo lipochinin.
However, in vitro, also oligosaccharides with a
GlcNAc residue at the reducing terminus and Lex
units are substrates [204].
10. Plants
A typical feature of plant N-glycans is the Xyl
L1,2-linked to the L-Man residue and an K1,3-linked
Fuc to the inner GlcNAc of the core (Fig. 6). Presently, peptide-N4 -(N-acetyl-L-glucosaminyl) asparagine amidase A from almond emulsin is the only
N-glycanase commercially available able to cleave
K1,3-core-fucosylated N-glycans from the peptide
backbone [205]. Since its introduction as a tool for
the analysis of plant glycans, it was found that this
kind of core K1,3-fucosylation is widespread in
plants. This is of particular interest since plant carbohydrates are involved in pollen and food allergy.
Both K1,3-linked Fuc and the Xyl form antigenic
epitopes which account for some IgE cross-reactions
between various plant, insect and mollusk extracts
[206^208]. However, the K1,3-Fuc linked to the innermost GlcNAc seems to be the most important
residue in the epitope [208,209].
A core K1,3-Fuc-T was puried from germinating
mung bean seedlings. The enzyme requires, similarly
to core K1,6-Fuc-Ts, the presence of an unsubstituted
GlcNAc residue linked to the K1,3-antenna of the
225
glycan. Neither type 1 nor type 2 structures serve

as acceptor substrates for the enzyme [210].
Another Fuc-T activity converting type 1 acceptors to Lea structures was also detected in mung
beans [211]. The corresponding structures with Lea
units on their antennae were identied from laccase,
puried from the culture medium of sycamore cells
(Acer pseudoplatanus L.) and from a peroxidase, puried from the culture medium of Vaccinium myrtillus L. cells [212,213]. Using anti-plant Lewis antibodies, Lea epitopes were detected in protein extracts of
various monocotyledonous, dicotyledonous and
gymnosperm plants, which suggests that the Lea epitope is more widely distributed than previously expected [212]. For an extensive review on N-glycan
biosynthesis in plants, see Lerouge et al. [214].
11. Relationships of Fuc-Ts
The detailed knowledge of eight human Fuc-T
genes and an increasing number of homologues
from other species has prompted various comparison
studies. Alignment studies for the identication of
highly conserved functional regions revealed that
mammalian K1,2- and K1,3-Fuc-Ts have a similar
predicted folding consisting of alternate K-helices
and L-strands [215]. In a further study, a nucleotide
binding region near the C-terminus and an acceptor
binding region near the N-terminus were assigned for
prokaryotic as well as eukaryotic enzymes [216]. Furthermore, homology studies gave the opportunity to
examine the evolution of Fuc-Ts by the creation of a
phylogenetic tree [119,217]. A recently published
study on the alignment of 78 Fuc-T protein sequences from vertebrates, invertebrates and bacteria supports the model that Fuc-Ts evolved from one, or
perhaps two, hypothetical ancestor gene(s), followed
by duplications and subsequent divergence [218].
12. Fucosylation and biotechnology
Fig. 6. Plant N-glycans.
The glycosylation potentials of insect cells are of

pharmaceutical interest. Due to their advantage in
terms of costs as well as of biosafety, lepidopteran
insect cell lines, mainly Spodoptera frugiperda, are
used for the baculovirus-mediated expression of re-
BBAGEN 24929 17-11-99
226
combinant proteins. Due to various factors, it is desirable to achieve a glycosylation pattern as much
alike to the mammalian pattern as possible. In particular non-mammalian features, such as the presence
of the plant-like K1,3-linked Fuc residue on the inner
GlcNAc, which is highly immunogenic [209], should
be avoided. The same problem has to be considered
when using plant cells or plants for the production of
pharmaceuticals.
Enzymatic synthesis and modication of oligosaccharides are very specic ways to produce well-dened glycans for biochemical and medical research
(e.g. selectin binding or allergenicity studies) [219].
All cloned human Fuc-Ts have been used towards
this end, e.g. [220^223]. In particular Fuc-T III has
been expressed in various systems, including the
methylotrophic yeast Pichia pastoris [224], and is
widely used for the synthesis of natural and non-natural glycans, e.g. [225^228].
Another application for glycosyltranferases is their
use for in vivo modulation of carbohydrate epitopes.
Mammals, except humans and old world monkeys,
express GalK1,3Gal units on glycans of their cell
surfaces. Therefore, xenotransplantation of porcine
organs to humans would immediately induce the production of antibodies against this epitope, with the
subsequent activation of the complement system. Besides the knockout of the porcine K1,3-galactosyltransferase, the expression of an additional K1,2Fuc-T is a promising way to modify the carbohydrates into non-immunogenic structures. The newly
introduced K1,2-Fuc-T co-localises with the K1,3-galactosyltransferase and competes for the same substrate. Also the K1,2-fucosylation is a `NOGO' signal
for K1,3-galactosylation [229^234]. However, only a
combination of more than one method, for example
the co-expression of K1,2-Fuc-T and an K-galactosidase, eectively reduces the expression of K-Gal to
negligible levels [235].
13. Future aspects
As discussed in the review, fucosylated structures
have proven to be involved in a number of intercellular recognition events, but the picture is still far
from clear. Further attempts have to be made to
elucidate changes of the glycosylation patterns dur-
ing pathological processes in order to take advantage

of unusual structures for site-specic drug targeting.
Interspecies interactions can also be aected by
fucosylation of oligosaccharides. Not only host-parasite interactions should be considered, but also the
possible use of glycoprotein therapeutics derived
from non-mammalian systems. Indeed, the increasing
use of cell culture for the production of recombinant
glycoproteins for therapeutic purposes forces industry to establish easier and cheaper systems, but care
should be taken that the glycans of the proteins produced are similar to those of the natural counterparts. The knowledge of glycosyltransferase genes
allows for the modication of glycans in vivo by
the additional expression of specic enzymes or by
knockout of endogenous enzymes. Genetic engineering of whole mammals which secrete the desired
product with their milk or are a potential source of
organs for xenotransplantation may prove a major
part of the future of biotechnology in this area.
14. Note added in proof
Recently, a sixth K1,3-Fuc-T (Fuc-T IX) has been
identied, which reveals high homology to the mouse
Fuk-T IX [236]. Furthermore, the rst K1,3-Fuc-T
catalysing the transfer of Fuc into K1,3-linkage to
the innermost GlcNAc-residue of a N-glycan was
cloned from mung beans and expressed in Sf 21 insect cells. Only one of its four exons exhibits signicant homology to the known animal and bacterial
K1,3/4-Fuc-Ts [237].
Acknowledgements
Research from our laboratory cited in this review
was supported by the Fonds zur Forderung der wissenschaftlichen Forschung (P 10611 GEN and P
sterreichische Hochschul12552 MOB) and by the O
jubilaumsstiftung.
References
[1] R. Kornfeld, S. Kornfeld, Assembly of asparagine-linked
oligosaccharides, Ann. Rev. Biochem. 54 (1985) 631^664.
BBAGEN 24929 17-11-99

[2] H. Schachter, Biosynthetic control that determine the
branching and microheterogeneity of protein-bound oligosaccharides, Biochem. Cell Biol. 64 (1986) 163^181.
[3] R.M. Bill, L. Reves and I.B.H. Wilson, Protein Glycosylation, Kluwer Academic Publishers, Boston, MA, 1998.
[4] H. Geyer, R. Geyer, Strategies for glycoconjugate analysis,
Acta Anat. (Basel) 161 (1998) 18^35.
[5] R.J. Harris, M.W. Spellman, O-linked fucose and other
post-translational modications unique to EGF modules,
Glycobiology 3 (1993) 219^224.
[6] F. Sinowatz, J. Plendl, S. Kolle, Protein-carbohydrate interactions during fertilization, Acta Anat. (Basel) 161 (1998)
196^205.
[7] M. Nakano, N. Yonezawa, Y. Hatanaka, S. Noguchi, Structure and function of the N-linked carbohydrate chains of pig
zona pellucida glycoproteins, J. Reprod. Fertil. Suppl. 50
(1996) 25^34.
[8] N. Yonezawa, S. Mitsui, K. Kudo, M. Nakano, Identication of an N-glycosylated region of pig zona pellucida glycoprotein ZPB that is involved in sperm binding, Eur. J.
Biochem. 248 (1997) 86^92.
[9] E. Mori, J.L. Hedrick, N.J. Wardrip, T. Mori, S. Takasaki,
Occurrence of reducing terminal N-acetylglucosamine 3-sulfate and fucosylated outer chains in acidic N-glycans of porcine zona pellucida glycoproteins, Glycoconjug. J. 15 (1998)
447^456.
[10] R. Lefebvre, M.C. Lo, S.S. Suarez, Bovine sperm binding to
oviductal epithelium involves fucose recognition, Biol. Reprod. 56 (1997) 1198^1204.
[11] D.S. Johnston, W.W. Wright, J.H. Shaper, C.H. Hokke,
D.H. VandenEijnden, D.H. Joziasse, Murine sperm-zona
binding, a fucosyl residue is required for a high anity
sperm-binding ligand - A second site on sperm binds a nonfucosylated, L-galactosyl-capped oligosaccharide, J. Biol.
Chem. 273 (1998) 1888^1895.
[12] H. Lucas, S. Bercegeay, J. LePendu, M. Jean, S. Mirelle, P.
Barriere, A fucose-containing epitope potentially involved in
gamete interaction on the human zona pellucida, Hum. Reprod. 9 (1994) 1532^1538.
[13] R. Talevi, R. Gualtieri, G. Tartaglione, A. Fortunato, Heterogeneity of the zona pellucida carbohydrate distribution in
human oocytes failing to fertilize in vitro, Hum. Reprod. 12
(1997) 2773^2780.
[14] S.S. Raychoudhury, C.F. Millette, Multiple fucosyltransferases and their carbohydrate ligands are involved in spermatogenic cell-Sertoli cell adhesion in vitro in rats, Biol. Reprod. 56 (1997) 1268^1273.
[15] S.S. Raychoudhury, C.F. Millette, Glycosidic specicity of
fucosyltransferases present in rat epididymal spermatozoa,
J. Androl. 16 (1995) 448^456.
[16] S. Chu, W.A. Walker, Developmental changes in the activities of sialyl- and fucosyltransferases in rat small intestine,
Biochim. Biophys. Acta 883 (1986) 496^500.
[17] D. Ruggiero-Lopez, C.M. Biol, P. Louisot, A. Martin,
Participation of an endogenous inhibitor of fucosyltransferase activities in the developmental regulation of in-
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
227
testinal fucosylation processes, Biochem. J. 279 (1991) 801^

806.
J. Xiang, I.A. Bernstein, Dierentiative changes in fucosyltransferase activity in newborn rat epidermal cells, Biochem.
Biophys. Res. Commun. 189 (1992) 27^32.
F. Tardy, P. Louisot, A. Martin, Ontogenic and nutritional
modications in the intestinal fucosylation process at the
weaning period. Inuence of dietary bers, Biochim. Biophys. Acta 1201 (1994) 41^50.
D. Lenoir, D. Ruggiero-Lopez, P. Louisot, M.C. Biol, Developmental changes in intestinal glycosylation: Nutritiondependent multi-factor regulation of the fucosylation pathway at weaning time, Biochim. Biophys. Acta 1234 (1995)
29^36.
M. Nemansky, N.R. Thotakura, C.D. Lyons, S. Ye, B.B.
Reinhold, V.N. Reinhold, D.L. Blithe, Developmental
changes in the glycosylation of glycoprotein hormone free
K-subunit during pregnancy, J. Biol. Chem. 273 (1998)
12068^12076.
J.B. Lowe, Carbohydrate recognition in cell-cell interaction,
in: M. Fukuda and O. Hindsgaul (Eds.), Molecular Glycobiology, Oxford University Press, Oxford, 1994, pp. 163^
205.
P.R. Crocker, T. Feizi, Carbohydrate recognition systems :
Functional triads in cell-cell interactions, Curr. Opin. Struct.
Biol. 6 (1996) 679^691.
J.B. Lowe, Selectin ligands, leukocyte tracking, and fucosyltransferase genes, Kidney Int. 51 (1997) 1418^1426.
C. Galustian, A.M. Lawson, S. Komba, H. Ishida, M. Kiso,
T. Feizi, Sialyl-Lewisx sequence 6-O-sulfated at N-acetylglucosamine rather than at galactose is the preferred ligand for
L-selectin and de-N-acetylation of the sialic acid enhances
the binding strength, Biochem. Biophys. Res. Commun.
240 (1997) 748^751.
K. Handa, M.R. Stroud, S. Hakomori, Sialosyl-fucosyl polyLacNAc without the sialosyl-Lex epitope as the physiological
myeloid cell ligand in E-selectin-dependent adhesion: Studies
under static and dynamic ow conditions, Biochemistry 36
(1997) 12412^12420.
E.L. Berg, A.T. Mullowney, D.P. Andrew, J.E. Goldberg,
E.C. Butcher, Complexity and dierential expression of carbohydrate epitopes associated with L-selectin recognition of
high endothelial venules, Am. J. Pathol. 152 (1998) 469^477.
M.-L. Majuri, M. Pinola, R. Niemela, S. Tiisala, J. Natunen,
O. Renkonen, R. Renkonen, K2,3-Sialyl and K1,3-fucosyltransferase-dependent synthesis of sialyl Lewisx , an essential
oligosaccharide present on L-selectin counterreceptors, in
cultured endothelial cells, Eur. J. Immunol. 24 (1994)
3205^3210.
E.V. Chandrasekaran, R.K. Jain, R.D. Larsen, K. Wlasichuk, R.A. DiCioccio, K.L. Matta, Specicity analysis of
three clonal and ve non-clonal K1,3-L-fucosyltransferases
with sulfated, sialylated, or fucosylated synthetic carbohydrates as acceptors in relation to the assembly of 3P-sialyl6P-sulfo Lewisx (the L-selectin ligand) and related complex
structures, Biochemistry 35 (1996) 8925^8933.
BBAGEN 24929 17-11-99
228
[30] R.N. Knibbs, R.A. Craig, S. Natsuka, A. Chang, M. Cameron, J.B. Lowe, L.M. Stoolman, The fucosyltransferase
FucT-VII regulates E-selectin ligand synthesis in human T
cells, J. Cell Biol. 133 (1996) 911^920.
[31] P. Maly, A.D. Thall, B. Petryniak, G.E. Rogers, P.L. Smith,
R.M. Marks, R.J. Kelly, K.M. Gersten, G.Y. Cheng, T.L.
Saunders, S.A. Camper, R.T. Camphausen, F.X. Sullivan,
Y. Isogai, O. Hindsgaul, U.H. vonAndrian, J.B. Lowe,
The K(1,3)fucosyltransferase Fuc-TVII controls leukocyte
tracking through an essential role in L-, E-, and P-selectin
ligand biosynthesis, Cell 86 (1996) 643^653.
[32] A.J. Wagers, J.B. Lowe, G.S. Kansas, An important role for
the K1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion
to E-selectin, Blood 88 (1996) 2125^2132.
[33] A.J. Wagers, L.M. Stoolman, R. Kannagi, R. Craig, G.S.
Kansas, Expression of leukocyte fucosyltransferases regulates binding to E-selectin - Relationship to previously implicated carbohydrate epitopes, J. Immunol. 159 (1997)
1917^1929.
[34] C.J. Britten, D.H. VandenEijnden, W. McDowell, V.A.
Kelly, S.J. Witham, M.R. Edbrooke, M.I. Bird, T. DeVries,
N. Smithers, Acceptor specicity of the human leukocyte K3
fucosyltransferase : role of FucT-VII in the generation of
selectin ligands, Glycobiology 8 (1998) 321^327.
[35] C.A. VanWely, A.D. Blanchard, C.J. Britten, Dierential
expression of K3 fucosyltransferases in Th1 and Th2 cells
correlates with their ability to bind P-selectin, Biochem. Biophys. Res. Commun. 247 (1998) 307^311.
[36] N. Hiraiwa, T. Dohi, N. Kawakami-Kimura, M. Yumen, K.
Ohmori, M. Maeda, R. Kannagi, Suppression of sialyl Lewisx expression and E-selectin-mediated cell adhesion in cultured human lymphoid cells by transfection of antisense
cDNA of an K1,3- fucosyltransferase (Fuc-T VII), J. Biol.
Chem. 271 (1996) 31556^31561.
[37] C. Galustian, R.A. Childs, C.T. Yuen, A. Hasegawa, M.
Kiso, A. Lubineau, G. Shaw, T. Feizi, Valency dependent
patterns of binding of human L-selectin toward sialyl and
sulfated oligosaccharides of Lea and Lex types: Relevance to
anti-adhesion therapeutics, Biochemistry 36 (1997) 5260^
5266.
[38] A. Koenig, R. Jain, R. Vig, K.E. Norgard-Sumnicht, K.L.
Matta, A. Varki, Selectin inhibition : Synthesis and evaluation of novel sialylated, sulfated and fucosylated oligosaccharides, including the major capping group of GlyCAM1, Glycobiology 7 (1997) 79^93.
[39] A.K. Sarkar, K.S. Rostand, R.K. Jain, K.L. Matta, J.D.
Esko, Fucosylation of disaccharide precursors of sialyl Lewisx inhibit selectin-mediated cell adhesion, J. Biol. Chem. 272
(1997) 25608^25616.
[40] K. Handa, D.A. Withers, S. Hakomori, The K1,3-fucosylation at the penultimate GlcNAc catalyzed by fucosyltransferase VII is blocked by internally fucosylated residue in
sialosyl long-chain poly-LacNAc: Enzymatic basis for expression of physiological E-selectin epitope, Biochem. Biophys. Res. Commun. 243 (1998) 199^204.
[41] R. Stahn, H. Schafer, F. Kernchen, J. Schreiber, Multivalent
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
sialyl Lewisx ligands of denite structures as inhibitors of Eselectin mediated cell adhesion, Glycobiology 8 (1998) 311^
319.
Y. Hiramatsu, H. Moriyama, T. Kiyoi, T. Tsukida, Y. Inoue, H. Kondo, Studies on selectin blockers. 6. Discovery of
homologous fucose sugar unit necessary for E-selectin binding, J. Med. Chem. 41 (1998) 2302^2307.
T. Muramatsu, Carbohydrate signals in metastasis and prognosis of human carcinomas, Glycobiology 3 (1993) 294^296.
M. Fukuda, Possible roles of tumor-associated carbohydrate
antigens, Cancer Res. 56 (1996) 2237^2244.
J. Ogawa, H. Inoue, S. Koide, Expression of K1,3-fucosyltransferase type IV and VII genes is related to poor prognosis in lung cancer, Cancer Res. 56 (1996) 325^329.
J. Ogawa, H. Inoue, S. Koide, K2,3-sialyltransferase type 3N
and K1,3-fucosyltransferase type VII are related to sialyl
Lewisx synthesis and patient survival from lung carcinoma,
Cancer 79 (1997) 1678^1685.
M. Mart|n-Satue, R. Marrugat, J.A. Cancelas, J. Blanco,
Enhanced expression of K(1,3)fucosyltransferase genes correlates with E-selectin-mediated adhesion and metastatic potential of human lung adenocarcinoma cells, Cancer Res. 58
(1998) 1544^1550.
M.L. Majuri, R. Niemela, S. Tiisala, O. Renkonen, R. Renkonen, Expression and function of K2,3-sialyl- and K1,3/1,4fucosyltransferases in colon adenocarcinoma cell lines : Role
in synthesis of E-selectin counter-receptors, Int. J. Cancer 63
(1995) 551^559.
C. Hanski, E. Klussmann, J. Wang, C. Bohm, D. Ogorek,
M.L. Hanski, S. Kruger-Krasagakes, J. Eberle, A. SchmittGra, E.O. Riecken, Fucosyltransferase III and sialyl-Lex
expression correlate in cultured colon carcinoma cells but
not in colon carcinoma tissue, Glycoconjug. J. 13 (1996)
727^733.
S. Nakamori, M. Kameyama, S. Imaoka, H. Furukawa, O.
Ishikawa, Y. Sasaki, Y. Izumi, T. Irimura, Involvement of
carbohydrate antigen sialyl Lewisx in colorectal cancer
metastasis, Dis. Colon Rectum 40 (1997) 420^431.
H. Ito, N. Hiraiwa, M. Sawada-Kasugai, S. Akamatsu, T.
Tachikawa, Y. Kasai, S. Akiyama, K. Ito, H. Takagi, R.
Kannagi, Altered mRNA expression of specic molecular
species of fucosyl- and sialyl-transferases in human colorectal cancer tissues, Int. J. Cancer 71 (1997) 556^564.
Y. Ikehara, S. Nishihara, T. Kudo, T. Hiraga, K. Morozumi, T. Hattori, H. Narimatsu, The aberrant expression of
Lewisa antigen in intestinal metaplastic cells of gastric mucosa is caused by augmentation of Lewis enzyme expression,
Glycoconjug. J. 15 (1998) 799^807.
T. Kudo, Y. Ikehara, A. Togayachi, K. Morozumi, M. Watanabe, M. Nakamura, S. Nishihara, H. Narimatsu, Up-regulation of a set of glycosyltransferase genes in human colorectal cancer, Lab. Invest. 78 (1998) 797^811.
C. Goupille, F. Hallouin, K. Meah, J. LePendu, Increase of
rat colon carcinoma cells tumorigenicity by K1,2-fucosyltransferase gene transfection, Glycobiology 7 (1997) 221^
229.
BBAGEN 24929 17-11-99

[55] M. Valli, A. Gallanti, S. Bozzaro, M. Trinchera, L1,3-galactosyltransferase and K1,2-fucosyltransferase involved in the
biosynthesis of type-1-chain carbohydrate antigens in human
colon adenocarcinoma cell lines, Eur. J. Biochem. 256 (1998)
494^501.
[56] E.V. Chandrasekaran, R.K. Jain, J.M. Rhodes, C.A. Srnka,
R.D. Larsen, K.L. Matta, Expression of blood group Lewisb
determinant from Lewisa : Association of this novel K1,2-Lfucosylating activity with the Lewis type K(1,3/4)-L-fucosyltransferase, Biochemistry 34 (1995) 4748^4756.
[57] J.I. Nakamura, A. Mogi, T. Asao, Y. Nagamachi, S. Yazawa, Evidence that the aberrant K1,2-fucosyltransferase found
in colorectal carcinoma may be encoded by Fuc-TIII (Le)
gene, Anticancer Res. 17 (1997) 4563^4569.
[58] W.L. Hutchinson, P.J. Johnson, M.-Q. Du, R. Williams,
Serum and tissue K-L-fucosidase activity in the pre-clinical
and clinical stages of hepatocellular carcinoma, Clin. Sci. 81
(1991) 177^182.
[59] M. Ohno, A. Nishikawa, M. Koketsu, H. Taga, Y. Endo, T.
Hada, K. Higashino, N. Taniguchi, Enzymatic basis of sugar
structures of K-fetoprotein in hepatoma and hepatoblastoma
cell lines: Correlation with activities of K1,6 fucosyltransferase and N-acetylglucosaminyltransferases III and V, Int. J.
Cancer 51 (1992) 315^317.
[60] J. Nakamura, S. Yazawa, T. Hada, T. Asao, H. Naitoh, S.
Takenoshita, M. Kosaka, S. Akamatsu, T. Tachikawa, Y.
Nagamachi, The usefulness of anti-fucosylated antigen antibody YB-2 for diagnosis of hepatocellular carcinoma, Glycoconjug. J. 14 (1997) 81^87.
[61] K. Noda, E. Miyoshi, N. Uozumi, S. Yanagidani, Y. Ikeda,
C.X. Gao, K. Suzuki, H. Yoshihara, M. Yoshikawa, K.
Kawano, N. Hayashi, M. Hori, N. Taniguchi, Gene expression of K1,6-fucosyltransferase in human hepatoma tissues:
A possible implication for increased fucosylation of K-fetoprotein, Hepatology 28 (1998) 944^952.
[62] K. Noda, E. Miyoshi, N. Uozumi, C.X. Gao, K. Suzuki, N.
Hayashi, M. Hori, N. Taniguchi, High expression of K1,6fucosyltransferase during rat hepatocarcinogenesis, Int. J.
Cancer 75 (1998) 444^450.
[63] Y. Aoyagi, Y. Suzuki, K. Igarashi, A. Saitoh, M. Oguro, T.
Yokota, S. Mori, M. Nomoto, M. Isemura, H. Asakura, The
usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of K-fetoprotein in the dierential diagnosis of neoplastic diseases of the liver, Cancer 67
(1991) 2390^2394.
[64] Y. Aoyagi, A. Saitoh, Y. Suzuki, K. Igarashi, M. Oguro, T.
Yokota, S. Mori, T. Suda, M. Isemura, H. Asakura, Fucosylation index of K-fetoprotein, a possible aid in the early
recognition of hepatocellular carcinoma in patients with cirrhosis, Hepatology 17 (1993) 50^52.
[65] V. Kudryashov, H.M. Kim, G. Ragupathi, S.J.. Danishefsky, P.O. Livingston, K.O. Lloyd, Immunogenicity of synthetic conjugates of Lewisy oligosaccharide with proteins in
mice : towards the design of anticancer vaccines, Cancer Immunol. Immunother. 45 (1998) 281^286.
229
[66] A. Kobata, A retrospective and prospective view of glycopathology, Glycoconjug. J. 15 (1998) 323^331.
[67] I. Brockhausen, J. Schutzbach, W. Kuhns, Glycoproteins
and their relationship to human disease, Acta Anat. 161
(1998) 36^78.
[68] P.J. Delves, The role of glycosylation in autoimmune disease, Autoimmunity 27 (1998) 239^253.
[69] J.J. Listinsky, G.P. Siegal, C.M. Listinsky, K-L-fucose - a
potentially critical molecule in pathologic processes including neoplasia, Am. J. Clin. Pathol. 110 (1998) 425^440.
[70] L. Russell, P. Waring, J.P. Beaver, Increased cell surface
exposure of fucose residues is a late event in apoptosis, Biochem. Biophys. Res. Commun. 250 (1998) 449^453.
[71] K. Hiraishi, K. Suzuki, S. Hakamori, M. Adachi, Ley antigen expression is correlated with apoptosis (programmed cell
death), Glycobiology 3 (1993) 381^390.
[72] S. Akamatsu, S. Yazawa, K. Zenita, H. Matsumoto, T. Tachikawa, R. Kannagi, Elevation of an K(1,3)fucosyltransferase activity correlated with apoptosis in the human colon
adenocarcinoma cell line, HT-29, Glycoconjug. J. 13 (1996)
1021^1029.
[73] P. Greenwell, Blood group antigens: Molecules seeking a
function?, Glycoconjug. J. 14 (1997) 159^173.
[74] W.M. Watkins, Molecular basis of antigenic specicity in the
AB0, H and Lewis blood group systems, in: J. Montreuil,
J.F.G. Vliegenthart and H. Schachter (Eds.), New Comprehensive Biochemistry, Vol. 29a, Glycoproteins, Elsevier Science B.V., Amsterdam, 1995, pp. 313^390.
[75] A. Sarnesto, T. Kohlin, O. Hindsgaul, J. Thurin, M. Blaszczyk-Thurin, Purication of the secretor-type L-galactoside
K1,2-fucosyltransferase from human serum, J. Biol. Chem.
267 (1992) 2737^2744.
[76] R.D. Larson, L.K. Ernst, R. Nair, J.B. Lowe, Molecular
cloning, sequence, and expression of a human GDP-L-fucose: L-D-galactoside 2-K-L-fucosyltransferase cDNA that
can form the H blood group antigen, Proc. Natl. Acad.
Sci. USA 87 (1990) 6674^6678.
[77] R.J. Kelly, S. Rouquier, D. Giorgi, G.G. Lennon, J.B.
Lowe, Sequence and expression of a candidate for the human Secretor blood group K(1,2)fucosyltransferase gene
(FUT2). Homozygosity for an enzyme-inactivating nonsense
mutation commonly correlates with the non-secretor phenotype, J. Biol. Chem. 270 (1995) 4640^4649.
[78] S. Henry, R. Mollicone, P. Fernandez, B. Samuelsson, R.
Oriol, G. Larson, Molecular basis for erythrocyte Le(a+b+)
and salivary ABH partial-secretor phenotypes: Expression of
a FUT2 secretor allele with an ACT mutation at nucleotide
385 correlates with reduced K(1,2)fucosyltransferase activity,
Glycoconjug. J. 13 (1996) 985^993.
[79] Y. Koda, M. Soejima, P.H. Johnson, E. Smart, H. Kimura,
Missense mutation of FUT1 and deletion of FUT2 are responsible for Indian Bombay phenotype of ABO blood
group system, Biochem. Biophys. Res. Commun. 238
(1997) 21^25.
[80] B.J. Wang, Y. Koda, M. Soejima, H. Kimura, Two missense
mutations of H type K(1,2)fucosyltransferase gene (FUT1)
BBAGEN 24929 17-11-99
230
[81]
[82]
[83]
[84]
[85]
[86]
[87]
[88]
[89]
[90]
[91]

responsible for para-Bombay phenotype, Vox Sang. 72
(1997) 31^35.
L.C. Yu, Y.H. Yang, R.E. Broadberry, Y.H. Chen, M. Lin,
Heterogeneity of the human H blood group K(1,2)fucosyltransferase gene among para-Bombay individuals, Vox Sang.
72 (1997) 36^40.
J.F. Kukowska-Latallo, R.D. Larsen, R.P. Nair, J.B. Lowe,
A cloned human cDNA determines expression of a mouse
stage-specic embryonic antigen and the Lewis blood group
K(1,3/1,4)fucosyltransferase, Genes Dev. 4 (1990) 1288^1303.
S.E. Goelz, C. Hession, D. Go, B. Griths, R. Tizard, B.
Newman, G. Chi-Rosso, R. Lobb, ELFT: a gene that directs
the expression of an ELAM-1 ligand, Cell 63 (1990) 1349^
1356.
J.B. Lowe, J.F. Kukowska-Latallo, R.P. Nair, R.D. Larsen,
R.M. Marks, B.A. Macher, R.J. Kelly, L.K. Ernst, Molecular cloning of a human fucosyltransferase gene that determines expression of the Lewisx and VIM-2 epitopes but not
ELAM-1-dependent cell adhesion, J. Biol. Chem. 266 (1991)
17467^17477.
R. Kumar, B. Potvin, W.A. Muller, P. Stanley, Cloning of a
human K(1,3)-fucosyltransferase gene that encodes ELFT
but does not confer ELAM-1 recognition on Chinese hamster ovary cell transfectants, J. Biol. Chem. 266 (1991)
21777^21783.
B.W. Weston, R.P. Nair, R.D. Larsen, J.B. Lowe, Isolation
of a novel human K(1,3)fucosyltransferase gene and molecular comparison to the human Lewis blood group K(1,3/
1,4)fucosyltransferase gene. Syntenic, homologous, nonallelic
genes encoding enzymes with distinct acceptor substrate specicities, J. Biol. Chem. 267 (1992) 4152^4160.
B.W. Weston, P.L. Smith, R.J. Kelly, J.B. Lowe, Molecular
cloning of a fourth member of a human K(1,3)fucosyltransferase gene family. Multiple homologous sequences that determine expression of the Lewisx , sialyl Lewisx , and difucosyl
sialyl Lewisx epitopes, J. Biol. Chem. 267 (1992) 24575^
24584.
K.L. Koszdin, B.R. Bowen, The cloning and expression of a
human K1,3-fucosyltransferase capable of forming the E-selectin ligand, Biochem. Biophys. Res. Commun. 187 (1992)
152^157.
S. Natsuka, K.M. Gersten, K. Zenita, R. Kannagi, J.B.
Lowe, Molecular cloning of a cDNA encoding a novel human leukocyte K1,3-fucosyltransferase capable of synthesizing the sialyl Lewisx determinant, J. Biol. Chem. 269 (1994)
16789^16794.
K. Sasaki, K. Kurata, K. Funayama, M. Nagata, E. Watanabe, S. Ohta, N. Hanai, T. Nishi, Expression cloning of a
novel K1,3-fucosyltransferase that is involved in biosynthesis
of the sialyl Lewisx carbohydrate determinants in leukocytes,
J. Biol. Chem. 269 (1994) 14730^14737.
R.S. McCurley, A. Recinos III, A.S. Olsen, J.C. Gingrich,
D. Szczepaniak, H.S. Cameron, R. Krauss and B.W. Weston, Physical maps of human K(1,3)fucosyltransferase genes
FUT3-FUT6 on chromosomes 19p13.3 and 11q21, Genomics, 1995, pp. 142^146.
[92] H. Schachter, Molecular cloning of glycosyltransferase

genes, in: M. Fukuda and O. Hindsgaul (Eds.), Molecular
Glycobiology. Oxford University Press, Oxford, 1994, pp.
88^162.
[93] B.A. Macher, E.H. Holmes, S.J. Swiedler, C.L.M. Stults,
C.A. Srnka, Human K1,3-fucosyltransferases, Glycobiology
1 (1991) 577^584.
[94] T. DeVries, D.H. VandenEijnden, Occurrence and specicities of K3-fucosyltransferases, Histochem. J. 24 (1992) 761^
770.
[95] E. Staudacher, K-1,3-fucosyltransferases, Trends Glycosci.
Glycotechnol. 8 (1996) 391^408.
[96] B.W. Murray, S. Takayama, J. Schultz, C.H. Wong, Mechanism and specicity of human K1,3-fucosyltransferase V,
Biochemistry 35 (1996) 11183^11195.
[97] O. Zollner, D. Vestweber, The E-selectin ligand-1 is selectively activated in Chinese hamster ovary cells by the
K(1,3)-fucosyltransferases IV and VII, J. Biol. Chem. 271
(1996) 33002^33008.
[98] J. Costa, E. Grabenhorst, M. Nimtz, H.S. Conradt, Stable
expression of the Golgi form and secretory variants of human fucosyltransferase III from BHK-21 cells - Purication
and characterization of an engineered truncated form from
the culture medium, J. Biol. Chem. 272 (1997) 11613^
11621.
[99] B.W. Murray, V. Wittmann, M.D. Burkart, S.C. Hung,
C.H. Wong, Mechanism of human K1,3-fucosyltransferase
V: Glycosidic cleavage occurs prior to nucleophilic attack,
Biochemistry 36 (1997) 823^831.
[100] T. DeVries, M.P. Palcic, P.S. Schoenmakers, D.H. VandenEijnden, D. Joziasse, Acceptor specicity of GDP-Fuc:
GalL1,4GlcNAc-R K3-fucosyltransferase VI (FucT VI) expressed in insect cells as soluble, secreted enzyme, Glycobiology 7 (1997) 921^927.
[101] K. Shinoda, Y. Morishita, K. Sasaki, Y. Matsuda, I. Takahashi, T. Nishi, Enzymatic characterization of human
K1,3-fucosyltransferase Fuc-TVII synthesized in a B cell
lymphoma cell lines, J. Biol. Chem. 272 (1997) 31992^
31997.
[102] N. Smithers, V.A. Kelly, S.J. Witham, M.R. Edbrooke,
C.J. Britten, Expression of a secreted form of human
K1,3 fucosyltranferase VII from insect cells, Biochem.
Soc. Trans. 25 (1997) 426S.
[103] L. Borsig, A.G. Katopodis, B.R. Bowen, E.G. Berger, Trafcking and localization studies of recombinant K1,3-fucosyltransferase VI stably expressed in CHO cells, Glycobiology 8 (1998) 259^268.
[104] H.S. Cameron, D. Szczepaniak, B.W. Weston, Expression
of human chromosome 19p K(1,3)-fucosyltransferase genes
in normal tissues - Alternative splicing, polyadenylation,
and isoforms, J. Biol. Chem. 270 (1995) 20112^20122.
[105] J.L. Clarke, W.M. Watkins, K1,3-L-Fucosyltransferase expression in developing human myeloid cells. Antigenic, enzymatic, and mRNA analyses, J. Biol. Chem. 271 (1996)
10317^10328.
[106] J.L. Clarke, W.M. Watkins, Independent regulation of Fuc-
BBAGEN 24929 17-11-99
[107]
[108]
[109]
[110]
[111]
[112]
[113]
[114]
[115]
[116]
[117]
TIV and Fuc-TVII genes leading to modulation of cell surface antigen expression in developing myeloid cells, Glycobiology 7 (1997) 835^846.
P. Cullen, S. Mohr, B. Brennhausen, A. Cignarella, G.
Assmann, Downregulation of the selectin ligand-producing
fucosyltransferases Fuc-TIV and Fuc-TVII during foam cell
formation in monocyte-derived macrophages, Arterioscler.
Thromb. Vasc. Biol. 17 (1997) 1591^1598.
N. LeMarer, M.M. Palcic, J.L. Clarke, D. Davies, P.O.
Skacel, Developmental regulation of K1,3-fucosyltransferase expression in CD34 positive progenitors and maturing
myeloid cells isolated from normal human bone marrow,
E.H. Holmes, Z. Xu, A.L. Sherwood, B.A. Macher, Structure-function analysis of human K1,3fucosyltransferases. A
GDP-fucose-protected, N-ethylmaleimide-sensitive site in
FucT-III and FucT-V corresponds to Ser178 in FucT-IV,
J. Biol. Chem. 270 (1995) 8145^8151.
D.J. Legault, R.J. Kelly, Y. Natsuka, J.B. Lowe, Human
K(1,3/1,4)-fucosyltransferases discriminate between dierent
oligosaccharide acceptor substrates through a discrete peptide fragment, J. Biol. Chem. 270 (1995) 20987^20996.
T. DeVries, C.A. Srnka, M.M. Palcic, S.J. Swiedler, D.H.
VandenEijnden, B.A. Macher, Acceptor specicity of dierent length constructs of human recombinant K1,3/4-fucosyltransferases. Replacement of the stem region and the transmembrane domain of fucosyltransferase V by protein A
results in an enzyme with GDP-fucose hydrolyzing activity,
J. Biol. Chem. 270 (1995) 8712^8722.
T.F. Orntoft, E.M. Vestergaard, E. Holmes, J.S. Jakobsen,
N. Grunnet, M. Mortensen, P. Johnson, P. Bross, N. Gregersen, K. Skorstengaard, U.B. Jensen, L. Bolund, H.
Wolf, Inuence of Lewis K1-3/4-L-fucosyltransferase
(FUT3) gene mutations on enzyme activity, erythrocyte
phenotyping, and circulating tumor marker sialyl-Lewisa
levels, J. Biol. Chem. 271 (1996) 32260^32268.
X.H. Xu, L. Vo, B.A. Macher, Structure-function analysis
of human K1,3-fucosyltransferase - Amino acids involved in
acceptor substrate specicity, J. Biol. Chem. 271 (1996)
8818^8823.
C.J. Britten, M.I. Bird, Chemical modication of an K3fucosyltransferase; Denition of amino acid residues essential for enzyme activity, Biochim. Biophys. Acta 1334
(1997) 57^64.
A. Elmgren, R. Mollicone, M. Costache, C. Borjeson, R.
Oriol, J. Harrington, G. Larson, Signicance of individual
point mutations, T202C and C314T, in the human Lewis
(FUT3) gene for expression of Lewis antigens by the human
K(1,3/1,4)-fucosyltransferase, Fuc-TIII, J. Biol. Chem. 272
(1997) 21994^21998.
A.T. Nguyen, E.H. Holmes, J.M. Whitaker, S. Ho, S. Shetterly, B.A. Macher, Human K1,3/4-fucosyltransferases - I.
Identication of amino acids involved in acceptor substrate
binding by site-directed mutagenesis, J. Biol. Chem. 273
(1998) 25244^25249.
L. Vo, S. Lee, M.C. Marcinko, E.H. Holmes, B.A. Macher,
[118]
[119]
[120]
[121]
[122]
[123]
[124]
[125]
[126]
[127]
[128]
[129]
231
Human K1,3/4-fucosyltransferases - II. A single amino acid

at the COOH terminus of FucT III and V alters their kinetic properties, J. Biol. Chem. 273 (1998) 25250^25255.
A.L. Sherwood, A.T. Nguyen, J.M. Whitaker, B.A. Macher, M.R. Stroud, E.H. Holmes, Human K1,3/4-fucosyltransferases - III. A Lys/Arg residue located within the K1,3FucT motif is required for activity but not substrate binding, J. Biol. Chem. 273 (1998) 25256^25260.
M. Costache, P.A. Apoil, A. Cailleau, A. Elmgren, G. Larson, S. Henry, S. Blancher, D. Iordachescu, R. Oriol, R.
Mollicone, Evolution of fucosyltransferase genes in vertebrates, J. Biol. Chem. 272 (1997) 29721^29728.
A. Oulmouden, A. Wierinckx, J.M. Petit, M. Costache,
M.M. Palcic, R. Mollicone, R. Oriol, R. Julien, Molecular
cloning and expression of a bovine K(1,3)-fucosyltransferase
gene homologous to a putative ancestor gene of the human
FUT3-FUT5-FUT6 cluster, J. Biol. Chem. 272 (1997) 8764^
8773.
K.M. Gersten, S. Natsuka, M. Trinchera, B. Petryniak,
R.J. Kelly, N. Hiraiwa, N. Jenkins, D.J. Gilbert, N.G. Copeland, J.B. Lowe, Molecular cloning, expression, chromosomal assignment, and tissue-specic expression of a murine K(1,3)-fucosyltransferase locus corresponding to the
human ELAM-1 ligand fucosyl transferase, J. Biol. Chem.
270 (1995) 25047^25056.
M. Ozawa, T. Muramatsu, Molecular cloning and expression of a mouse K1,3 fucosyltransferase gene that shows
homology with the human K1,3 fucosyltransferase IV
gene, J. Biochem. (Tokyo) 119 (1996) 302^308.
E.M. Sajdel-Sulkowska, F.I. Smith, G. Wiederschain, R.H.
McCluer, Cloning of a rat K1,3-fucosyltransferase gene: A
member of the fucosyltransferase IV family, Glycoconjug.
J. 14 (1997) 249^258.
P.L. Smith, K.M. Gersten, B. Petryniak, R.J. Kelly, C.
Rogers, Y. Natsuka, J.A. Alford III, E.P. Scheidegger, S.
Natsuka, J.B. Lowe, Expression of the K(1,3)-fucosyltransferase Fuc-TVII in lymphoid aggregate high endothelial
venules correlates with expression of L-selectin ligands,
J. Biol. Chem. 271 (1996) 8250^8259.
T. Kudo, Y. Ikehara, A. Togayachi, M. Kaneko, T. Hiraga, K. Sasaki, H. Narimatsu, Expression cloning and
characterization of a novel murine K1,3-fucosyltransferase,
mFuc-TIX, that synthesizes the Lewisx (CD15) epitope in
brain and kidney, J. Biol. Chem. 273 (1998) 26729^26738.
S.S. Raychoudhury, C.F. Millette, Presence of multiple fucosyltransferases in rat Sertoli cells and spermatogenic cells,
Biol. Reprod. 51 (1994) 1006^1013.
V. Karaivanova, S. Mookerjea, D. Hunt, A. Nagpurkar,
Characterization and purication of fucosyltransferases
from the cytosol of rat colon, Int. J. Biochem. Cell Biol.
28 (1996) 165^174.
C. Campbell, P. Stanley, The chinese hamster ovary glycosylation mutants LEC11 and LEC12 express two novel
GDP-fucose:N-acetylglucosamide 3-K-L-fucosyltransferase
enzymes, J. Biol. Chem. 258 (1984) 11208^11214.
B. Potvin, P. Stanley, Activation of two new K(1,3)fucosyl-
BBAGEN 24929 17-11-99
232
[130]
[131]
[132]
[133]
[134]
[135]
[136]
[137]
[138]
[139]
[140]
[141]
[142]
[143]

transferase activities in Chinese hamster ovary cells by 5azacytidine, Cell Regul. 2 (1991) 989^1000.
B. Potvin, R. Kumar, D.R. Howard, P. Stanley, Transfection of a human K-(1,3)fucosyltransferase gene into chinese
hamster ovary cells, J. Biol. Chem. 265 (1990) 1615^1622.
J.L. Clarke, W.M. Watkins, Three dierent endogenous KL-fucosyltransferases expressed in COS cells, Biochem. Biophys. Res. Commun. 237 (1997) 400^406.
S. Hitoshi, S. Kusunoki, I. Kanazawa, S. Tsuji, Molecular
cloning and expression of two types of rabbit L-galactoside
K1,2-fucosyltransferase, J. Biol. Chem. 270 (1995) 8844^
8850.
S. Hitoshi, S. Kusunoki, I. Kanazawa, S. Tsuji, Molecular
cloning and expression of a third type of rabbit GDP-Lfucose:L-D-galactoside 2-K-L-fucosyltransferase, J. Biol.
Chem. 271 (1996) 16975^16981.
S. Hitoshi, S. Kusunoki, I. Kanazawa, S. Tsuji, Dorsal root
ganglia-specic expression of the L-galactoside K1,2-fucosyltransferase genes in rabbits, J. Neurochem. 70 (1998)
2174^2178.
J.-P. Piau, N. Labarriere, G. Dabouis, M.G. Denis, Evidence for two distinct K(1,2)-fucosyltransferase genes dierentially expressed throughout the rat colon, Biochem. J.
300 (1994) 623^626.
S.E. Domino, N. Hiraiwa, J.B. Lowe, Molecular cloning,
chromosomal assignment and tissue-specic expression of a
murine K(1,2)fucosyltransferase expressed in thymic and
epididymal epithelial cells, Biochem. J. 327 (1997) 105^
115.
S. Cohney, E. Mouhtouris, I.F.C. McKenzie, M.S. Sandrin,
Molecular cloning of the gene coding for pig K1,2fucosyltransferase, Immunogenetics 44 (1996) 76^79.
J. Thurin, M. Blaszczyk-Thurin, Porcine submaxillary
gland GDP-L-fucose:L-D-galactoside K-2-L-fucosyltransferase is likely a counterpart of the human Secretor gene-encoded blood group transferase, J. Biol. Chem. 270 (1995)
26577^26580.
A. Kobata, Structures and functions of the sugar chains of
glycoproteins, Eur. J. Biochem. 209 (1992) 483^501.
T. Noronkoski, I. Mononen, Inuence of L-fucose attached
K1,6 to the asparagine-linked N-acetylglucosamine on the
hydrolysis of the N-glycosidic linkage by human glycosylasparaginase, Glycobiology 7 (1997) 217^220.
N. Kojima, Y. Tachida, Y. Yoshida, S. Tsuji, Characterization of mouse ST8Sia II (STX) as a neural cell adhesion
molecule-specic polysialic acid synthase - Requirement of
core K1,6-linked fucose and a polypeptide chain for polysialylation, J. Biol. Chem. 271 (1996) 19457^19463.
J.R. Wilson, D. Williams, H. Schachter, The control of
glycoprotein synthesis. N-acetylglucosamine linkage to a
mannose residue as a signal for the attachment of L-fucose
to the asparagine-linked N-acetylglucosamine of glycopeptides from K1 -acid glycoprotein, Biochem. Biophys. Res.
Commun. 72 (1976) 909^916.
G.D. Longmore, H. Schachter, Product-identication and
substrate-specicity studies of the GDP-L-fucose:2-acetami-
[144]
[145]
[146]
[147]
[148]
[149]
[150]
[151]
[152]
[153]
[154]
[155]
do-2-deoxy-L-glucoside (FucCAsn-linked GlcNAc) 6-K-Lfucosyltransferase in a golgi-rich fraction from porcine liver, Carbohydr. Res. 100 (1982) 365^392.
J.A. Voynow, R.S. Kaiser, T.F. Scanlin, M.C. Glick, Purication and characterization of GDP-L-fucose-N-acetyl-LD-glucosaminide K1C6fucosyltransferase from cultured human skin broblasts. Requirement of a specic biantennary
oligosaccharide as substrate, J. Biol. Chem. 266 (1991)
21572^21577.
N. Uozumi, S. Yanagidani, E. Miyoshi, Y. Ihara, T. Sakuma, C.X. Gao, T. Teshima, S. Fujii, T. Shiba, N. Taniguchi, Purication and cDNA cloning of porcine brain GDPL-Fuc: N-acetyl-L-D-glucosaminide K1C6fucasyltransferase, J. Biol. Chem. 271 (1996) 27810^27817.
S. Yanagidani, N. Uozumi, Y. Ihara, E. Miyoshi, N.
Yamaguchi, N. Taniguchi, Purication and cDNA cloning
of GDP-L-Fuc:N-acetyl-L-D-glucosaminide: K1-6 fucosyltransferase (K1-6 FucT) from human gastric cancer
MKN45 cells, J. Biochem. (Tokyo) 121 (1997) 626^632.
J. Kaminska, M.C. Glick, J. Koscielak, Purication and
characterization of GDP-L-Fuc: N-acetyl-L-D-glucosaminide K1,6-fucosyltransferase from human blood platelets,
Glycoconjug. J. 15 (1998) 783^788.
A.I. Lin, G.A. Philipsberg, R.S. Haltiwanger, Core fucosylation of high-mannose-type oligosaccharides in GlcNAc
transferase I-decient (Lec1) CHO cells, Glycobiology 4
(1994) 895^901.
T. Endo, T. Fujiwara, Y. Ikehara, A. Kobata, Comparative
study of the sugar chains of alkaline phosphatases puried
from rat liver and rat AH-130 hepatoma cells - Occurrence
of fucosylated high-mannose-type and hybrid-type sugar
chains, Eur. J. Biochem. 236 (1996) 579^590.
Y.J. Chen, D.R. Wing, G.R. Guile, R.A. Dwek, D.J. Harvey, S. Zamze, Neutral N-glycans in adult rat brain tissue Complete characterisation reveals fucosylated hybrid and
complex structures, Eur. J. Biochem. 251 (1998) 691^703.
Y. Shikata, H. Ohe, N. Mano, M. Kuwada, N, Asakawa,
Structural analysis of N-linked carbohydrate chains of
funnel web spider (Agelenopsis aperta) venom peptide
isomerase, Biosci. Biotechnol. Biochem. 62 (1998) 1211^
1215.
A. Vitale, M.J. Chrispeels, Transient N-acetylglucosamine
in the biosynthesis of phytohemagglutinin: attachment in
the golgi apparatus and removal in protein bodies, J. Cell
Biol. 99 (1984) 133^140.
F. Altmann, H. Schwihla, E. Staudacher, J. Glossl, L.
Marz, Insect cells contain an unusual, membrane-bound
L-N-acetylglucosaminidase probably involved in the processing of protein N-glycans, J. Biol. Chem. 270 (1995)
17344^17349.
J.J. Priatel, M. Sarkar, H. Schachter, J.D. Marth, Isolation,
characterization and inactivation of the mouse Mgat3 gene:
The bisecting N-acetylglucosamine in asparagine-linked oligosaccharides appears dispensable for viability and reproduction, Glycobiology 7 (1997) 45^56.
E. Staudacher, L. Marz, Strict order of (Fuc to Asn-linked
BBAGEN 24929 17-11-99
[156]
[157]
[158]
[159]
[160]
[161]
[162]
[163]
[164]
[165]
[166]
[167]
GlcNAc) fucosyltransferases forming core-difucosylated

structures, Glycoconjug. J. 15 (1998) 355^360.
N. Uozumi, T. Teshima, T. Yamamoto, A. Nishikawa,
Y.E. Gao, E. Miyoshi, C.X. Gao, K. Noda, K.N. Islam,
Y. Ihara, S. Fujii, T. Shiba, N. Taniguchi, A uorescent
assay method for GDP-L-Fuc:N-acetyl-L-D-glucosaminide
K1,6fucosyltransferase activity, involving high performance
liquid chromatography, J. Biochem. (Tokyo) 120 (1996)
385^392.
A. Roitinger, H. Leiter, E. Staudacher, F. Altmann, HPLC
method for the determination of Fuc to Asn-linked
GlcNAc fucosyltransferases, Glycoconjug. J. 15 (1998)
89^91.
V. Kubelka, F. Altmann, E. Staudacher, V. Tretter, L.
Marz, K. Hard, J.P. Kamerling, J.F.G. Vliegenthart, Primary structures of the N-linked carbohydrate chains from
honeybee venom phospholipase A2 , Eur. J. Biochem. 213
(1993) 1193^1204.
E. Staudacher, F. Altmann, L. Marz, K. Hard, J.P. Kamerling, J.F.G. Vliegenthart, K1-6(K1-3)-Difucosylation of
the asparagine-bound N-acetylglucosamine in honeybee
venom phospholipase A2 , Glycoconjug. J. 9 (1992) 82^85.
V. Kubelka, F. Altmann, L. Marz, The asparagine-linked
carbohydrate of honeybee venom hyaluronidase, Glycoconjug. J. 12 (1995) 77^83.
V. Kubelka, F. Altmann, G. Kornfeld, L. Marz, Structures
of the N-linked oligosaccharides of the membrane glycoproteins from three lepidopteran cell lines (Sf-21, IZDMb-0503, Bm-N), Arch. Biochem. Biophys. 308 (1994)
148^157.
K.H. Khoo, D. Chatterjee, J.P. Cauleld, H.R. Morris, A.
Dell, Structural mapping of the glycans from the egg glycoproteins of Schistosoma mansoni and Schistosoma japonicum: Identication of novel core structures and terminal
sequences, Glycobiology 7 (1997) 663^677.
S.M. Haslam, G.C. Coles, E.A. Munn, T.S. Smith, H.F.
Smith, H.R. Morris, A. Dell, Haemonchus contortus glycoproteins contain N-linked oligosaccharides with novel
highly fucosylated core structures, J. Biol. Chem. 271
(1996) 30561^30570.
R.A. Siciliano, H.R. Morris, R.A. McDowell, P. Azadi,
M.E. Rogers, H.P.J. Bennett, A. Dell, The Lewisx epitope
is a major non-reducing structure in the sulphated N-glycans attached to Asn-65 of bovine pro-opiomelanocortin,
A.A. Bergwer, J.E. Thomas-Oates, J. VanOostrum, J.P.
Kamerling, J.F.G. Vliegenthart, Human urokinase contains
GalNAcL(1-4)[FucK(1-3)]GlcNAcL(1-2) as a novel terminal
element in N-linked carbohydrate chains, FEBS Lett. 314
(1992) 389^394.
S.B. Yan, Y.B. Chao, H. VanHalbeek, Novel Asn-linked
oligosaccharides terminating in GalNAcL(1C4)[FucK(1C3)]GlcNAcL(1CW) are present in recombinant human
Protein C expressed in human kidney 293 cells, Glycobiology 3 (1993) 597^608.
J. Srivatsan, D.F. Smith, R.D. Cummings, Schistosoma
[168]
[169]
[170]
[171]
[172]
[173]
[174]
[175]
[176]
[177]
[178]
[179]
[180]
[181]
233
mansoni synthesizes novel biantennary Asn-linked oligosaccharides containing terminal L-linked N-acetylgalactosamine, Glycobiology 2 (1992) 445^452.
G. Lochnit, R. Geyer, Carbohydrate structure analysis of
batroxobin, a thrombin-like serine protease from Bothrops
moojeni venom, Eur. J. Biochem. 228 (1995) 805^816.
E. Staudacher, V. Kubelka, L. Marz, Distinct N-glycan
fucosylation potentials of three lepidopteran cell lines,
Eur. J. Biochem. 207 (1992) 987^993.
E. Staudacher, F. Altmann, J. Glossl, L. Marz, H.
Schachter, J.P. Kamerling, K. Hard, J.F.G. Vliegenthart,
GDP-fucose: L-N-acetylglucosamine (Fuc to (FucK1C6GlcNAc)Asn-peptide) K1C3-fucosyltransferase activity in
honeybee (Apis mellica) venom glands - The difucosylation of asparagine-bound N-acetylglucosamine, Eur. J. Biochem. 199 (1991) 745^751.
L. Marz, F. Altmann, E. Staudacher and V. Kubelka,
Protein glycosylation in insects, in: J. Montreuil, J.F.G.
Vliegenthart and H. Schachter (Eds.), New Comprehensive
Biochemistry, Vol 29b, Glycoproteins, Elsevier Science
B.V., Amsterdam, 1995, pp. 163^172.
F. Altmann, Glycosylation in insects revisited, Trends Glycosci. Glycotechnol. 8 (1996) 101^114.
F. Altmann, More than silk and honey - or, can insect cells
serve in the production of therapeutic glycoproteins?, Glycoconjug. J. 14 (1997) 643^646.
F. Altmann, E. Staudacher, I.B.H. Wilson, L. Marz, Insect
cells as hosts for the expression of recombinant glycoproteins, Glycoconjug. J. 16 (1999) 109^123.
J.A. vanKuik, H. vanHalbeek, J.P. Kamerling, J.F.G.
Vliegenthart, Primary structure of the low-molecular-weight
carbohydrate chains of Helix pomatia K-hemocyanin,
J. Biol. Chem. 260 (1985) 13984^13988.
J.A. vanKuik, R.P. Sijbesma, J.P. Kamerling, J.F.G.
Vliegenthart, E.J. Wood, Primary structure determination
of seven novel N-linked carbohydrate chains derived from
hemocyanin of Lymnea stagnalis, Eur. J. Biochem. 169
(1987) 399^411.
J.P.M. Lommerse, J.E. Thomas-Oates, C. Gielens, G. Preaux, J.P. Kamerling, J.F.G. Vliegenthart, Primary structure
of 21 novel monoantennary and diantennary N-linked carbohydrate chains from KD -hemocyanin of Helix pomatia,
Eur. J. Biochem. 249 (1997) 195^222.
H. Mulder, H. Schachter, J.R. Thomas, K.M. Halkes, J.P.
Kamerling, J.F.G. Vliegenthart, Identication of a GDPFuc:GalL1-3GalNAc-R (Fuc to Gal) K1-2 fucosyltransferase and a GDP-Fuc:GalL1-4GlcNAc (Fuc to GlcNAc) K13 fucosyltransferase in connective tissue of the snail Lymnaea stagnalis, Glycoconjug. J. 13 (1996) 107^113.
R.D. Cummings, A.K. Nyame, Glycobiology of schistosomiasis, FASEB J. 10 (1996) 838^848.
A.K. Nyame, J.B. Pilcher, V.C.W. Tsang, R.D. Cummings,
Schistosoma mansoni infection in humans and primates induces cytolytic antibodies to surface Lex determinants on
myeloid cells, Exp. Parasitol. 82 (1996) 191^200.
R. DeBose-Boyd, A.K. Nyame, R.D. Cummings, Schisto-
BBAGEN 24929 17-11-99
234
[182]
[183]
[184]
[185]
[186]
[187]
[188]
[189]
[190]
[191]
[192]
[193]

soma mansoni: Characterization of an K1-3 fucosyltransferase in adult parasites, Exp. Parasitol. 82 (1996) 1^10.
K.-H. Khoo, S. Sarda, X. Xu, J.P. Cauleld, M.R. McNeil,
S.W. Homans, H.R. Morris, A. Dell, A unique multifucosylated -3GalNAcL1C4GlcNAcL1C3GalK1- motif constitutes the repeating unit of the complex O-glycans derived
from the cercarial glycocalyx of Schistosoma mansoni,
J. Biol. Chem. 270 (1995) 17114^17123.
K.H. Khoo, D. Chatterjee, J.P. Cauleld, H.R. Morris, A.
Dell, Structural characterization of glycosphingolipids from
the eggs of Schistosoma mansoni and Schistosoma japonicum, Glycobiology 7 (1997) 653^661.
C.H. Hokke, A.P. Neeleman, C.A.M. Koeleman, D.H.
VandenEijnden, Identication of an K3-fucosyltransferase
and a novel K2-fucosyltransferase activity in cercariae of
the schistosome Trichobilharzia ocellata: biosynthesis of
the
FucK1C2FucK1C3[Gal(NAc)L1C4]GlcNAc
sequence, Glycobiology 8 (1998) 393^406.
A.K. Nyame, R. DeBose-Boyd, T.D. Long, V.C.W. Tsang,
R.D. Cummings, Expression of Lex antigen in Schistosoma
japonicum and S-haematobium and immune responses to
Lex in infected animals: lack of Lex expression in other
trematodes and nematodes, Glycobiology 8 (1998) 615^624.
R.A. DeBose-Boyd, A.K. Nyame, R.D. Cummings, Molecular cloning and characterization of an K1,3 fucosyltransferase, CEFT-1, from Caenorhabditis elegans, Glycobiology
8 (1998) 905^917.
R.A. DeBose-Boyd, A.K. Nyame, D.P. Jasmer, R.D. Cummings, The ruminant parasite Haemonchus contortus expresses an K1,3-fucosyltransferase capable of synthesizing
the Lewisx and sialyl Lewisx antigens, Glycoconjug. J. 15
(1998) 789^798.
G.R. Riley, G.M. West, E.J. Henderson, Cell dierentiation in Dictyostelium discoideum controls assembly of protein-linked glycans, Glycobiology 3 (1993) 165^177.
A. Champion, K. Griths, A.A. Gooley, B.Y. Gonzalez,
M. Gritzali, C.M. West, K.L. Williams, Immunochemical,
genetic and morphological comparison of fucosylation mutants of Dictyostelium discoideum, Microbiology 141 (1995)
785^797.
G. Srikrishna, L.Y. Wang, H.H. Freeze, FucoseL-1-P-Ser is
a new type of glycosylation: using antibodies to identify a
novel structure in Dictyostelium discoideum and study multiple types of fucosylation during growth and development,
B. Gonzalez-Yanes, J.M. Cicero, R.D. Brown Jr., C.M.
West, Characterization of a cytosolic fucosylation pathway
in Dictyostelium, J. Biol. Chem. 267 (1992) 9595^9605.
M. Trinchera, S. Bozzaro, Dictyostelium cytosolic fucosyltransferase synthesizes H type 1 trisaccharide in vitro,
FEBS Lett. 395 (1996) 68^72.
C.M. West, T. Scott-Ward, P. Teng-umnuay, H. VanderWel, E. Kozarov, A. Huynh, Purication and characterization of an K1,2-L-fucosyltransferase, which modies the cytosolic protein FP21, from the cytosol of Dictyostelium,
J. Biol. Chem. 271 (1996) 12024^12035.
[194] K.P. Lee, L.M. Carlson, J.B. Woodcock, N. Ramachandra,

T.L. Schultz, T.A. Davis, J.B. Lowe, C.B. Thompson, R.D.
Larsen, Molecular cloning and characterization of CFT1, a
developmentally regulated avian K(1,3)-fucosyltransferase
gene, J. Biol. Chem. 271 (1996) 32960^32967.
[195] P.M. Jacquinot, D. Leger, J.M. Wieruszeski, B. Coddeville,
J. Montreuil, G. Spik, Change in glycosylation of chicken
transferrin glycans biosynthesized during embryogenesis
and primary culture of embryo hepatocytes, Glycobiology
4 (1994) 617^624.
[196] Y. Funakoshi, T. Taguchi, C. Sato, K. Kitajima, S. Inoue,
H.R. Morris, A. Dell, Y. Inoue, Occurrence of terminal
K2C8-linked disialylated poly-N-acetyllactosamine chains
with Lex and I antigenic glycotopes in tetraantennary
arms of an N-linked glycoprotein isolated from rainbow
trout ovarian uid, Glycobiology 7 (1997) 195^205.
[197] Y. Zhang, T. Iwasa, M. Tsuda, A. Kobata, S.A. Takasaki,
A novel monoantennary complex-type sugar chain found in
octopus rhodopsin occurrence of the GalL1C3Fuc group
linked to the proximal N-acetylglucosamine residue of the
trimannosyl core, Glycobiology 7 (1998) 1153^1158.
[198] G. Strecker, Amphibian glycoproteins, in: J. Montreuil,
J.F.G. Vliegenthart and H. Schachter (Eds.), New Comprehensive Biochemistry, Vol. 29b, Glycoproteins, Elsevier Science B.V., Amsterdam, 1997, pp. 163^172.
gren, I.M. Frick, D. Kersulyte,
[199] D. Ilver, A. Arnqvist, J. O
E.T. Incecik, D.E. Berg, A. Covacci, L. Engstrand, T. Boren, Helicobacter pylori adhesin binding fucosylated histoblood group antigens revealed by retagging, Science 279
(1998) 373^377.
[200] B.J. Appelmelk, I. Simoons-Smit, R. Negrini, A.P. Moran,
G.O. Aspinall, J.G. Forte, T. DeVries, H. Quan, T. Verboom, J.J. Maaskant, P. Ghiara, E.J. Kuipers, E. Bloemena, T.M. Tadema, R.R. Townsend, K. Tyagarajan, J.M.
Crothers Jr., M.A. Monteiro, A. Savio, J. De Graa, Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity, Infect. Immun. 64 (1996) 2031^2040.
[201] G.O. Aspinall, M.A. Monteiro, Lipopolysaccharides of
Helicobacter pylori strains P466 and MO19: Structures of
the O-antigen and core oligosaccharide regions, Biochemistry 35 (1996) 2498^2504.
[202] S.L. Martin, M.R. Edbrooke, T.C. Hodgman, D.H. VandenEijnden, M.I. Bird, Lewisx biosynthesis in Helicobacter
pylori - Molecular cloning of an K(1,3)-fucosyltransferase
gene, J. Biol. Chem. 272 (1997) 21349^21356.
[203] Z.M. Ge, N.W.C. Chan, M.M. Palcic, D.E. Taylor, Cloning and heterologous expression of an K1,3-fucosyltransferase gene from the gastric pathogen Helicobacter pylori,
J. Biol. Chem. 272 (1997) 21357^21363.
[204] C. Quinto, A.H.M. Wijfjes, G.V. Bloemberg, L. Blok-Tip,
I.M. Lopez-Lara, B.J.J. Lugtenberg, J.E. Thomas-Oates,
H.P. Spaink, Bacterial nodulation protein NodZ is a chitin
oligosaccharide fucosyltransferase which can also recognize
related substrates of animal origin, Proc. Natl. Acad. Sci.
USA 94 (1997) 4336^4341.
BBAGEN 24929 17-11-99

[205] V. Tretter, F. Altmann, L. Marz, Peptide-N4 -(N-acetyl-Lglucosaminyl)asparagine amidase F cannot release glycans
with fucose attached K1C3 to the asparagine-linked Nacetylglucosamine residue, Eur. J. Biochem. 199 (1991)
647^652.
[206] R.C. Aalberse, R. VanRee, Crossreactive carbohydrate determinants, Clin. Rev. Allergy Immunol. 15 (1997) 375^387.
[207] G. Garcia-Casado, R. Sanchez-Monge, M.J. Chrispeels, A.
Armentia, G. Salcedo, L. Gomez, Role of complex asparagine-linked glycans in the allergenicity of plant glycoproteins, Glycobiology 6 (1996) 471^477.
[208] I.B.H. Wilson, J.E. Harthill, N.P. Mullin, D.A. Ashford, F.
Altmann, Core K1,3-fucose is a key part of the epitope
recognized by antibodies reacting against plant N-linked
oligosaccharides and is present in a wide variety of plant
extracts, Glycobiology 8 (1998) 651^661.
[209] V. Tretter, F. Altmann, V. Kubelka, L. Marz, W.M. Becker, Fucose K1,3-linked to the core region of glycoprotein Nglycans creates an important epitope for IgE from honeybee venom allergic individuals, Int. Arch. Allergy Immunol.
102 (1993) 259^266.
[210] E. Staudacher, T. Dalik, P. Wawra, F. Altmann, L. Marz,
Functional purication and characterization of a GDP-fucose L-N-acetylglucosamine (Fuc to Asn linked GlcNAc)
K1,3-fucosyltransferase from mung beans, Glycoconjug. J.
12 (1995) 780^786.
[211] S.C. Crawley, O. Hindsgaul, R.M. Ratclie, L.R. Lamontagne, M.M. Palcic, A plant fucosyltransferase with human
Lewis blood-group specicity, Carbohydr. Res. 193 (1989)
249^256.
[212] A.C. Fitchette-Laine, V. Gomord, M. Cabanes, J.C. Michalski, M. SaintMacary, B. Foucher, B. Cavelier, C.
Hawes, P. Lerouge, L. Faye, N-glycans harboring the Lewisa epitope are expressed at the surface of plant cells, Plant
J. 12 (1997) 1411^1417.
[213] N.S. Melo, M. Nimtz, H.S. Conradt, P.S. Fevereiro, J.
Costa, Identication of the human Lewisa carbohydrate
motif in a secretory peroxidase from a plant cell suspension
culture (Vaccinium myrtillus L.), FEBS Lett. 415 (1997)
186^191.
[214] P. Lerouge, M. Cabanes-Macheteau, C. Rayon, A.C. Fichette-Laine, V. Gomord, L. Faye, N-glycoprotein biosynthesis in plants: recent developments and future trends, Plant
Mol. Biol. 38 (1998) 31^48.
[215] C. Breton, R. Oriol, A. Imberty, Sequence alignment and
fold recognition of fucosyltransferases, Glycobiology 6
(1996) VII^XII.
[216] C. Breton, R. Oriol, A. Imberty, Conserved structural features in eukaryotic and prokaryotic fucosyltransferases,
[217] M.R. Edbrooke, C.J. Britten, V.A.M. Kelly, S.L. Martin,
N. Smithers, A.J. Winder, S.J. Witham, M.I. Bird, The K(13)-fucosyltransferases come of age, Biochem. Soc. Trans. 25
(1997) 880^886.
[218] R. Oriol, R. Mollicone, A. Cailleau, L. Balanzino, C. Breton, Divergent evolution of fucosyltransferase genes from
[219]
[220]
[221]
[222]
[223]
[224]
[225]
[226]
[227]
[228]
[229]
[230]
[231]
235
vertebrates, invertebrates, and bacteria, Glycobiology 9

(1999) 323^334.
Z.M. Guo, P.G. Wang, Utilization of glycosyltransferases
to change oligosaccharide structures, Appl. Biochem. Biotechnol. 68 (1997) 1^20.
hrlein, A. Katopodis, M. Strei, F. KolG. Baisch, R. O
binger, Synthetic potential of cloned fucosyl-transferase III
and VI, Bioorg. Med. Chem. Lett. 7 (1997) 2447^2450.
H. Kimura, N. Shinya, S. Nishihara, M. Kaneko, T. Irimura, H. Narimatsu, Distinct substrate specicities of ve
human K1,3-fucosyltransferases for in vivo synthesis of the
sialyl Lewisx and Lewisx epitopes, Biochem. Biophys. Res.
Commun. 237 (1997) 131^137.
M.M. Palcic, H. Li, D. Zanini, R.S. Bhella, R. Roy, Chemoenzymatic synthesis of dendritic sialyl Lewisx , Carbohydr. Res. 305 (1997) 433^442.
M.R. Stroud, E.H. Holmes, Fucosylation of complex glycosphingolipids by recombinant fucosyltransferase-VII,
Biochem. Biophys. Res. Commun. 238 (1997) 165^168.
P.R. Gallet, H. Vaujour, J.M. Petit, A. Maftah, A. Oulmouden, R. Oriol, C. LeNarvor, M. Guilloton, R. Julien,
Heterologous expression of an engineered truncated form
of human Lewis fucosyltransferase (Fuc-TIII) by the methylotrophic yeast Pichia pastoris, Glycobiology 8 (1998) 919^
925.
J. Rabina, J. Natunen, R. Niemela, H. Salminen, K. Ilves,
O. Aitio, H. Maaheimo, J. Helin, O. Renkonen, Enzymatic
synthesis of site-specically K1,3-fucosylated polylactosamines containing either a sialyl Lewisx , a VIM-2, or a
sialylated and internally difucosylated sequence, Carbohydr. Res. 305 (1997) 491^499.
H. Salminen, K. Ahokas, R. Niemela, L. Penttila, H. Maaheimo, J. Helin, C.E. Costello, O. Renkonen, Improved
enzymatic synthesis of a highly potent oligosaccharide antagonist of L-selectin, FEBS Lett. 419 (1997) 220^226.
K. Stangier, M.M. Palcic, D.R. Bundle, O. Hindsgaul, J.
Thiem, Fucosyltransferase-catalyzed formation of L-galactosylated Lewis structures, Carbohydr. Res. 305 (1997)
511^515.
hrlein, M. Strei, Enzymatic fucosylations
G. Baisch, R. O
of non-natural sialylated type-I trisaccharides with recombinant fucosyl-transferase-III, Bioorg. Med. Chem.
Lett. 8 (1998) 161^164.
A. Sharma, J. Okabe, P. Birch, S.B. McClellan, M.J. Martin, J.L. Platt, J.S. Logan, Reduction in the level of
Gal(K1,3)Gal in transgenic mice and pigs by the expression
of an K1,2-fucosyltransferase, Proc. Natl. Acad. Sci. USA
93 (1996) 7190^7195.
S. Cohney, I.F.C. McKenzie, K. Patton, J. Prenzoska, K.
Ostenreid, W.L. Fodor, M.S. Sandrin, Down-regulation of
Ga1K(1,3)Gal expression by K1,2-fucosyltransferase - Further characterization of K1,2-fucosyltransferase transgenic
mice, Transplantation 64 (1997) 495^500.
C. Koike, A. Katayama, K. Kadomatsu, N. Hiraiwa, S.
Hayashi, T. Kobayashi, S. Hayash, I. Yokoyama, H. Takagi, Reduction of K-Gal epitopes in transgenic pig by in-
BBAGEN 24929 17-11-99
236
troduction of human K1-2 fucosyltransferase, Transplant.

Proc. 29 (1997) 894.
[232] T.A. Shinkel, C.G. Chen, E. Salvaris, T.R. Henion, H.
Barlow, U. Galili, M.J. Pearse, A.J.F. D'Apice, Changes
in cell surface glycosylation in K1,3-galactosyltransferase
knockout and K1,2-fucosyltransferase transgenic mice,
Transplantation 64 (1997) 197^204.
[233] C.G. Chen, E.J. Salvaris, M. Romanella, A. Aminian, M.
Katerelos, N. Fisicaro, A.J.F. D'Apice, M.J. Pearse, Transgenic expression of human K1,2-fucosyltransferase (Htransferase) prolongs mouse heart survival in an ex vivo
model of xenograft rejection, Transplantation 65 (1998)
832^837.
[234] P.J. Cowan, C.G. Chen, T.A. Shinkel, N. Fisicaro, E. Salvaris, A. Aminian, M. Romanella, M.J. Pearse, A.J.F.
D'Apice, Knock out of K1,3-galactosyltransferase or expression of K1,2-fucosyltransferase further protects CD55-
and CD59-expressing mouse hearts in an ex vivo model of

xenograft rejection, Transplantation 65 (1998) 1599^1604.
[235] N. Osman, I.F.C. McKenzie, K. Ostenried, Y.A. Ioannou,
R.J. Desnick, M.S. Sandrin, Combined transgenic expression of K-galactosidase and K1,2-fucosyltransferase leads to
optimal reduction in the major xenoepitope GalK(1,3)Gal,
Proc. Natl. Acad. Sci. USA 94 (1997) 14677^14682.
[236] M. Kaneko, T. Kudo, H. Iwasaki, Y. Ikehara, S. Nishihara, S. Nakagawa, K. Sasaki, T. Shiina, H. Inoko, N.
Saitou, H. Narimatsu, K1,3-Fucosyltransferase IX (Fuc-T
IX) is very highly conserved between human and mouse ;
molecular cloning, characterization and tissue distribution
of human Fuc-T IX, FEBS Lett. 452 (1999) 237^242.
[237] H. Leiter, J. Mucha, E. Staudacher, R. Grimm, J. Glossl,
F. Altmann, Purication, cDNA cloning, and expression of
GDP-L-Fuc: Asn-linked GlcNAc K1,3-fucosyltransferase
from mung beans, J. Biol. Chem. 274 (1999) 21830^21839.
BBAGEN 24929 17-11-99

Fucose in N-Glycans - From Plant To Man

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Fucose in N-Glycans - From Plant To Man

Uploaded by

Copyright:

Available Formats

Biochimica et Biophysica Acta 1473 (1999) 216^236

Fucose in N-glycans: from plant to man

2. Fucosylation of N-glycans in mammals . . . . . . . .

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

6. Trematodes and nematodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8. Fucosylation in other animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11. Relationships of Fuc-Ts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12. Fucosylation and biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

13. Future aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

14. Note added in proof . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

identied. Now, more than 150 entries of complete

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

ing, until adult patterns appeared, inuenced also by

terminal Gals, K1,3 or K1,4 to subterminal GlcNAc

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

this area. The great number of resulting publications

lines, only Se-type K1,2-Fuc-T was expressed [55]. In

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

carcinoma Colo 205 cells. The enzyme reveals a

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

tion of these enzymes. For instance, the chimpanzee

Rats and mice contain both analogues to human

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

Fuc-T is inhibited by prior K1,3-fucosylation of the

Fig. 2. Fucosylated insect N-glycans.

The rst analysis of a snail N-glycan was carried

Fig. 3. Fucosylated N-glycans from snails. (a) H. pomatia [175],

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

corresponding K1,3-fucosylated glycans have been

Fig. 4. Fucosylated N-glycans of helminths. (a) S. mansoni

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

Fig. 5. N-glycan from octopus rhodopsin [197].

was found on a N-glycan from octopus rhodopsin

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

glycan. Neither type 1 nor type 2 structures serve

Fig. 6. Plant N-glycans.

The glycosylation potentials of insect cells are of

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

ing pathological processes in order to take advantage

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

testinal fucosylation processes, Biochem. J. 279 (1991) 801^

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

[92] H. Schachter, Molecular cloning of glycosyltransferase

BBAGEN 24929 17-11-99

E. Staudacher et al. / Biochimica et Biophysica Acta 1473 (1999) 216^236

Human K1,3/4-fucosyltransferases - II. A single amino acid

BBAGEN 24929 17-11-99