Signal Transduction: Pathways, Mechanisms and Diseases

Anotherareacoveredinthisbook,onenotoftenhighlightedinsignaltransd- tionbooks,isthatofsignalingplatforms,whichisemergingasasigni?cantareaof researchrelevanttocellularmetabolism,cellproliferation,differentiation,apop- sis,neurodegenerativediseases,andcancer. Theauthorscontributingtothisbook vii viii Preface areexpertsandactivecontributorstoresearchintheirspeci?careasofsignaling. I would like to thank them for their contributions and their suggestions in the developmentofthebook. IwouldliketoacknowledgethehelpofFrankTedeschi, astudentinmydepartment,whoassistedineditingthemanuscriptsandinprep- ingtheindex. IwouldalsoliketothankDr. SabineSchwarz,LifeSciencesEditorat SpringerVerlag,andDr. JuttaLindenbornwhohavebeenveryhelpfulatevery stageofproductionofthisbook. AriSitaramayya Contents PartI GProteinsandGProtein–CoupledReceptors 1 TraditionalGPCRPharmacologyandBeyond. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 AnnetteGilchristandMariaR. Mazzoni 2 RegulationofIntraneuronalTraf?ckingofG-Protein-Coupled ReceptorsbyNeurotransmittersInVivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Ve´roniqueBernard 3 SmallGTPasesandTheirRoleinRegulatingGProtein-Coupled ReceptorSignalTransduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 FabiolaM. RibeiroandStephenS. G. Ferguson 4 RegulationofGProteinReceptorCoupling,MoodDisorders andMechanismofActionofAntidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 MoranGolan,GabrielSchreiber,andSo?aAvissar 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 2þ 13 MolecularandFunctionalDeterminantsofCa 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 ˆ ´ MichelB. Toledano,SimonFourquet,andBeno?tD’Autreaux 18 SolubleGuanylylCyclase:TheNitricOxideReceptor. . . . . . . . . . .

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 the current research interest, but also anticipates those areas that will continue to be of interest over the next several years.

The health-relatedness of research was a major criterion for selection, as can be seen in the list of topics covered, such as G protein coupled receptors, growth factors, nuclear receptors, reactive oxygen and nitrogen species, the cell cycle and cancer. The emphasis is on areas of signaling research with direct clinical significance. Another field covered, one rarely highlighted in signal transduction books, is that of signaling platforms, which has been emerging as a significant research area relevant to cellular metabolism, cell proliferation, differentiation, apoptosis, neurodegenerative diseases, and cancer.