Table Of ContentSignal Transduction: Pathways, Mechanisms
and Diseases
Ari Sitaramayya
Editor
Signal Transduction:
Pathways, Mechanisms
and Diseases
Editor
AriSitaramayya
ProfessorofBiomedicalSciences
423DHE
EyeResearchInstitute
OaklandUniversity
Rochester,MI48309
USA
[email protected]
ISBN978-3-642-02111-4 e-ISBN978-3-642-02112-1
DOI10.1007/978-3-642-02112-1
SpringerHeidelbergDordrechtLondonNewYork
LibraryofCongressControlNumber:2009928304
#Springer-VerlagBerlinHeidelberg2010
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Coverillustration:CellularandsubcellulardetectionofM2receptorsinstriatalneurons;seeFig.2.1in
Chap.2‘‘RegulationofIntraneuronalTraffickingofG-Protein-CoupledReceptorsbyNeurotransmitters
InVivo’’byVe´roniqueBernard
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ForUsha,Vani,andAruna
Preface
Teaching a graduate course on signal transduction in the fall of 2007 was very
enjoyable. Each week, my students and I discussed a recently published research
paperinsomeareaofsignaling,arguedabouttheappropriatenessofthemethodol-
ogy used in the research, the design of the experiments, and whether the conclu-
sions drawn were supported by the results presented. Finally, each student was
askedtolistwhatwasgoodandwhatwasdeficientinthepaperandwhethershe/he
would have accepted or rejected it had she/he reviewed it for publication. For a
good number ofrecentpapers, aconsistent complaint ofthe students was that the
backgroundtotheresearchwasnotadequatelydescribed.Itcanofcoursebeargued
that students should research the background. Either way, the need for a good
source of background material in order to appreciate the research presented in a
paperbecameapparenttomeandwastheinspirationfordevelopingthisbook.
The goal inbringingthis book was toprovide students with a review ofrecent
developmentsinspecificareasofcurrentinterestinsignaltransduction,sufficiently
indepthtomakerecentresearchpublicationsaccessible. However,giventhewide
range of research topics being investigated today in signaling, a choice had to be
madetofocusonaselectfew.Thischoicewasmadenotonlykeepingthecurrent
research interest in mind, but also with the anticipation that these areas will
continuetobeofinterestoverthenextseveralyears.
Inchoosingpapersfordiscussioninmyclass,Ilookforhealth-relatednessofthe
research,andthatisreflectedinthelistofthebroadareascoveredinthisbook–G
protein coupled receptors, growth factors, nuclear receptors, reactive oxygen and
nitrogenspecies,cellcycleandcancer;theemphasishasbeenonareasofsignaling
researchwithimmediateclinicalsignificance.Ibelievethisbookwillservewellas
supplementalreadingmaterialforundergraduateandgraduatestudentswithsimilar
interest.
Anotherareacoveredinthisbook,onenotoftenhighlightedinsignaltransduc-
tionbooks,isthatofsignalingplatforms,whichisemergingasasignificantareaof
researchrelevanttocellularmetabolism,cellproliferation,differentiation,apopto-
sis, neurodegenerative diseases, and cancer. The authors contributingto this book
vii
viii Preface
are experts and active contributors to research in their specific areas of signaling.
I would like to thank them for their contributions and their suggestions in the
developmentofthebook.IwouldliketoacknowledgethehelpofFrankTedeschi,
astudentinmydepartment,whoassistedineditingthemanuscriptsandinprepar-
ingtheindex.IwouldalsoliketothankDr.SabineSchwarz,LifeSciencesEditorat
Springer Verlag, and Dr. Jutta Lindenborn who have been very helpful at every
stageofproductionofthisbook.
AriSitaramayya
Contents
PartI GProteinsandGProtein–CoupledReceptors
1 TraditionalGPCRPharmacologyandBeyond ............................ 3
AnnetteGilchristandMariaR.Mazzoni
2 RegulationofIntraneuronalTraffickingofG-Protein-Coupled
ReceptorsbyNeurotransmittersInVivo ................................. 25
Ve´roniqueBernard
3 SmallGTPasesandTheirRoleinRegulatingGProtein-Coupled
ReceptorSignalTransduction ............................................. 43
FabiolaM.RibeiroandStephenS.G.Ferguson
4 RegulationofGProteinReceptorCoupling,MoodDisorders
andMechanismofActionofAntidepressants ............................ 63
MoranGolan,GabrielSchreiber,andSofiaAvissar
5 DysregulationofGProtein-CoupledReceptorSignaling
inCancer .................................................................... 83
JoAnnTrejo
PartII GrowthFactors
6 InsulinSignalinginNormalandDiabeticConditions ................. 101
PatriceEFort,HisanoriImai,RajuRajala,andThomasW.Gardner
7 EpidermalGrowthFactor(EGF)ReceptorSignaling
andCancer ................................................................ 119
ElizabethS.HensonandSpencerB.Gibson
ix
x Contents
8 LeptinSignalingPathway ............................................... 143
HiroyukiShimizu
9 SignalinginNormalandPathologicalAngiogenesis .................. 159
MichaelR.MancusoandCalvinJ.Kuo
PartIII SignalingPlatforms
10 SpatialandTemporalControlofCellSignaling
byA-KinaseAnchoringProteins ....................................... 183
F.DonelsonSmith,LoreneK.Langeberg,andJohnD.Scott
11 Mitochondria,aPlatformforDiverseSignalingPathways .......... 199
AstridC.SchaussandHeidiM.McBridee
12 Mitogen-ActivatedProteinKinases
andTheirScaffoldingProteins ......................................... 219
DannyN.DhanasekaranandE.PremkumarReddy
13 MolecularandFunctionalDeterminantsofCa2þ
SignalingMicrodomains ................................................ 237
InduS.Ambudkar,HweiL.Ong,andBrijB.Singh
PartIV NuclearReceptors/Transcription
14 EukaryoticGeneTranscription ........................................ 257
JenniferH.GromekandArikDvir
15 EstrogenSignalingMechanisms ........................................ 273
DapengZhangandVanceL.Trudeau
16 SignalTransductionPathwaysInvolved
inGlucocorticoidActions ............................................... 289
PeterJ.Barnes
PartV ReactiveSignalingMolecules
17 CellularSignalingbyReactiveOxygenSpecies:Biochemical
BasisandPhysiologicalScope .......................................... 313
MichelB.Toledano,SimonFourquet,andBenoˆıtD’Autre´aux
18 SolubleGuanylylCyclase:TheNitricOxideReceptor ............... 337
DorisKoeslingandAriSitaramayya
Contents xi
PartVI CellCycle,CellDeathandCancer
19 DistinctRolesofthePocketProteinsintheControl
ofCellCycle .............................................................. 353
ParaskeviVogiatziandPierPaoloClaudio
20 Activationofthep53TumorSuppressoranditsMultipleRoles
inCellCycleandApoptosis ............................................. 375
LucianaE.GionoandJamesJ.Manfredi
21 AgingandCancer:CaretakersandGatekeepers ..................... 397
DianavanHeemst
22 SignalTransductioninEmbryonicStemCells
andtheRiseofiPSCells ................................................ 417
SoleneJamet,RuairiFriel,andP.JosephMee
Index ......................................................................... 427
Description:This book was adapted from graduate courses on signal transduction taught by the editor, where the need for a good overview of recent developments on each of the topics being discussed became apparent. Given the wide range of research topics in signaling, a selection was made that not only reflects
