Chapter 16.

Cell Communication
A Simple Intracellular Signaling Pathway Activated by an
Extracellular Signal Molecule
Each Cell is Programmed to Respond to Specific Combinations of
Extracellular Signal Molecules
Geneticallydeterminedproteinsynthesisequipsspecialized
cellstorespondselectivelytoexternalsignals.
Different Cells Can Respond Differently to the Same
Extracellular Signal Molecule
Ways that animal cells use to signal one another
Extracellular signal molecules
binds either to cell surface
receptors or to intracellular
enzymes or receptors
The role of nitric oxide (NO) in smooth muscle
relaxation in a blood vessel wall
Hydrophobic Hormones
Some Hormone Receptors Are Gene Regulatory Proteins.
Three classes of cell-surface receptors.
Signaling pathways
All G-protein-linked receptors possess a similar structure
G-Protein-Linked Receptors Rely on Trimeric G-protein
Disassembly to Relay Signals
The switching off of the G-protein subunit by the
hydrolysis of its bound GTP
A Gi protein directly couples receptor activation to the opening of K+
channels in the plasma membrane of heart muscle cells
Enzymes activated by G proteins catalyze the synthesis of
intracellular second-messenger molecules
Two major signaling pathways activated though G-
protein-linked receptor
SomeGproteinsSignal
ByRegulatingthe
ProductionofCyclicAMP
Adrenaline stimulates glycogen breakdown in skeletal muscle cells
Gene Transcription is Activated by a Rise in cAMP Concentration
Two major signaling pathways activated though G-
protein-linked receptor
Some G proteins Activate the Inositol Phospholipid
Signaling Pathway by Activating Phospholipase C
Signaling pathways
Subunit dimerization mechanism for activation of
a receptor tyrosine kinase.
The activation of Ras by an activated receptor tyrosine kinase
Ras activates a MAP kinase phosphorylation cascade
RTKs can sctivate the PI-3-kinase Akt signaling pathway
Activated Akt promotes cell survival
Mutant proteins can help to determine exactly
where an intracellular signaling molecule binds
 Genetic analysis reveals the order in which
intracellular signaling proteins act in a pathway
Chapter 16 Cell Communication
Overall Objective: Understandhowthecellperceivessignalsfromtheenvironmentandhowthisinformationispassedontovarious
componentswithinthecell.

Specific Objectives:
1)BeabletoexplainhowheterotrimericG-proteinswork,including:Signaltransmission,activation,inactivation,andinteractionwithtargets
3)Knowwhatsecondmessengersareandhowtheyaregenerated.
4)Understandhowareceptortyrosinekinasefunctionsininitiatingasignaltransductionpathway
5)KnowtheroleofrasandMAPkinasesinthesepathways
6)Recognizefundamentalsimilaritiesinhowmanyreceptorsfunctiontocontroltranscriptionfactoractivity.

Note:Therearealotoffigures,butmanyarevariationsoncommonthemes.Trytoextractthecommonalitiesratherthantheminordifferences.
Thesameholdstruefortheproblems.

Problems:16-1,16-3,16-4,16-5,16-6,16-10,16-11,16-12,16-15(don'tworrytoomuchaboutgettingthisonesolvedonyourown,butmake
sureyouunderstandtheiranswer),16-16,16-17,16-18,16-19,16-22.

Advice:Usethehow we know sectiontotestyourunderstanding.Trytoimagewhatkindsofmolecularchangestothesignalingmolecules

couldcausetheeffectsdescribedinFigs16-36,16-38.Trytoimagesimilartypesofmutationsinothersignaling(ortransportCh15)pathways.
Seeproblems16-5,16-16,16-22.
Lecture Outline
Chapter 16 Cell Signaling
Means of signaling
Endocrine,paracrine,neuronal,contact-dependent

Intracellular receptors and signals.

NO(nitricoxide)
Steroidhormonesandreceptors.
Controloftranscription
Extracellular receptors
Classesofeukaryoticcellsurfacereceptors:
Ion-channel-linked
G-protein-linked
Enzyme-linked
Details:
G-protein coupled receptors7transmembranedomains
G-proteins:alpha,beta,gammasubunits.Lipidmodifications
Activationandinteractionwithtargetmolecules
Choleratoxin,pertussistoxin.
Ionchannels,enzymes
Enzymesandformationof2ndmessengers
Second messengers
cAMP,IP3,DAG,Ca2+
rolesofPKA,PKC,

Ca2+ and calmodulin

Receptor tyrosine Kinases:

ActivationofRas
MAPkinasecascades