Professional Documents
Culture Documents
2007
Cell Signaling
Transduction
Cascade
Something
Output
happens
©2002 Lee Bardwell
Responses to cell signaling
Something
happens biochemically
• Gene expression is altered at the level of
transcription, RNA processing or translation
• Enzyme activities are altered
• Protein-protein interactions are induced or
inhibited
• The localization of certain proteins and other
stuff is altered
Signal
(steroid)
Receptor
(txn factor)
Steroid Hormone Signaling Pathway
Output
∆ gene expression
∆ cell physiology
Signaling cascades have many steps
Past: Now:
Enumerate • Modules
components • Circuits/
Design Logic
• Cross-talk
• Specificity
Adrenaline
signaling
• Signal: Adrenaline (epinephrine)
– Secreted by adrenal gland
• Response:
– Breakdown of glycogen to glucose to
provide energy for “fight-or-flight”
Insulin
signaling
• Signal: insulin
– Secreted by β cells of pancreas
• Receptor: a receptor kinase
• Response:
– Sugar is taken up from bloodstream into
cells
• Diabetes - type 1, type 2
Growth factor signaling
The growth of multicellular organisms is
regulated by more than just nutrient availability
NUTRIENTS
unicellular
eukaryote
NUTRIENTS
multicellular
eukaryote
a edigner
Cells in multicellular eukaryotes require
permission signals from growth factors
NUTRIENTS
NUTRIENTS
a edigner
Disregulation of growth factor signal
transduction leads to cancer
NUTRIENTS
NUTRIENTS
cellular
transformation
Some growth factors
Kinase
PP P
ATP
Substrate
Protein Kinase Reaction
Phosphorylation of protein substrates
PP P
Product
Phosphorylation can flip a protein from
“active” to “inactive” or vis-versa
ATP
ADP
The Mitogen-Activated Protein Kinase
(MAPK) Cascade
RAF
P P
MEK MEK
P P
TXY TXY
MAPK MAPK
P P
SP TP SP TP
g r o w th fa c to r
HER2
re c e p to r
Ras
MEKK Raf
M E K /M A P K K
MEK1 MEK2
MAPKs
E R K 1E R K 2
E lk 1 /S R F F o s J u n c y c lin D 1
F O S
N e o p la s tic p h e n o ty p e
C C N D 1
Specificity in MAPK Signalling
How do protein
kinases recognize
their protein
substrates ?
Protein Kinase Reaction
Kinase
PP P
ATP
Substrate
Protein Kinase Reaction
Phosphorylation of protein substrates
PP P
Product
Active site - target peptide interaction
is not enough for specificity
Kinase
Substrate
Tethering function: Grewal et al (2006) Cell.
Bardwell Lab
• Lee Bardwell
• Jane Bardwell
• Kandarp Shah
• Lamar Blackwell
• Tom Whisenant
• Jeff Rogers
• Pascal Krotee