Arrestins - Pharmacology and Therapeutic Potential PDF
Preview Arrestins - Pharmacology and Therapeutic Potential
Handbook of Experimental Pharmacology 219 Vsevolod V. Gurevich Editor Arrestins - Pharmacology and Therapeutic Potential Handbook of Experimental Pharmacology Volume 219 Editor-in-Chief W. Rosenthal, Berlin Editorial Board J.E. Barrett, Philadelphia J. Buckingham, Uxbridge V. Flockerzi, Homburg F.B. Hofmann, Mu¨nchen P. Geppetti, Florence M.C. Michel, Ingelheim P. Moore, Singapore C.P. Page, London For furthervolumes: http://www.springer.com/series/164 . Vsevolod V. Gurevich Editor Arrestins - Pharmacology and Therapeutic Potential Editor VsevolodV.Gurevich ProfessorofPharmacology VanderbiltUniversityMedicalCenter Nashville Tennessee USA ISSN0171-2004 ISSN1865-0325(electronic) ISBN978-3-642-41198-4 ISBN978-3-642-41199-1(eBook) DOI10.1007/978-3-642-41199-1 SpringerHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2013955574 ©Springer-VerlagBerlinHeidelberg2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Thefirstarrestinwasdiscoveredinthevisualsystemasakeyplayerintheshutoff of prototypical G protein-coupled receptor (GPCR) rhodopsin. Cloning and func- tionalcharacterizationofitshomologuesrevealedthatspecificbindingofarrestin to the active phosphorylated forms of the great majority of GPCRs stops their G protein-mediatedsignaling.Arrestinsareaveragesized~45kDaproteinswiththe fold shared with (and probably inherited from) proteins involved in vesicle traf- ficking.Arrestinfamilyisfairlysmall:vertebratesexpressfoursubtypes,whereas otherbranchesoftheanimalkingdomhaveevenfewerdifferentarrestins.Yetthese few arrestins not only bind hundreds of GPCR subtypes expressed in virtually all animals but also interact with dozens of non-receptor-signaling proteins. Some of these interactions occur regardless of receptor binding, some are promoted by it, whileothersareprecludedorsuppressedbyGPCRinteraction.Thisplacesarrestins at an important intersection of signaling pathways in the cell where external and internal inputs are integrated into coherent behavior. This volume describes our current understanding of the biological role of visual and nonvisual arrestins in different cellsandtissues,focusingonthemechanismsofarrestin-mediated regu- lation of GPCRs and non-receptor-signaling proteins in health and disease. This bookcoversawiderangeofarrestinfunctions,emphasizingtherapeuticpotentialof targetingarrestininteractionswithindividualpartners.Arrestinsareultimatescaf- folds:theyorganizemultiproteinsignalingcomplexesandlocalizethemtopartic- ularcellularcompartments.Everythingarrestinsdoismediatedbyprotein–protein interactions.Sincehighlyregulatedprotein–proteininteractionsunderliemostvital cell functions, arrestins are a perfect proving ground for designing novel protein- basedtherapeutictoolstochannelcellsignalinginthedesireddirection. Nashville,TN VsevolodV.Gurevich v . Contents TherapeuticPotentialofSmallMoleculesand EngineeredProteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 EugeniaV.GurevichandVsevolodV.Gurevich PartI ArrestinsandRegulationofGProtein-CoupledReceptors ArrestinInteractionswithGProtein-CoupledReceptors. . . . . . . . . . . . 15 MartinJ.LohseandCarstenHoffmann QuantifyingBiasedβ-ArrestinSignaling. . . . . . . . . . . . . . . . . . . . . . . . 57 TerryKenakin ThePhysiologicalRolesofArrestin-1inRod PhotoreceptorCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 JeannieChen NotJustSignalShutoff:TheProtectiveRoleofArrestin-1in RodCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 MarthaE.Sommer,KlausPeterHofmann,andMartinHeck ConeArrestin:DecipheringtheStructureandFunctionsofArrestin 4inVision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 CherylMaeCraftandJaniseD.Deming EnhancedPhosphorylation-IndependentArrestins andGeneTherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 VsevolodV.Gurevich,XiufengSong,SergeyA.Vishnivetskiy, andEugeniaV.Gurevich TargetingIndividualGPCRswithRedesigned NonvisualArrestins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 LuisE.Gimenez,SergeyA.Vishnivetskiy,andVsevolodV.Gurevich vii viii Contents PartII ArrestinInteractionswithNon-receptorPartnersandRoles inCellSignaling β-ArrestinsandGProtein-CoupledReceptorTrafficking. . . . . . . . . . . 173 XufanTian,DongSooKang,andJeffreyL.Benovic ArrestinInteractionwithE3UbiquitinLigasesandDeubiquitinases: FunctionalandTherapeuticImplications. . . . . . . . . . . . . . . . . . . . . . . . 187 SudhaK.Shenoy Self-AssociationofArrestinFamilyMembers. . . . . . . . . . . . . . . . . . . . 205 QiuyanChen,YaZhuo,MiyeonKim,SusanM.Hanson,DerekJ.Francis, SergeyA.Vishnivetskiy,ChristianAltenbach,CandiceS.Klug, WayneL.Hubbell,andVsevolodV.Gurevich Arrestin-DependentActivationofERKandSrcFamilyKinases. . . . . . 225 ErikG.StrungsandLouisM.Luttrell Arrestin-DependentActivationofJNKFamilyKinases. . . . . . . . . . . . . 259 XuanzhiZhan,SeunghyiKook,EugeniaV.Gurevich, andVsevolodV.Gurevich Arrestin-MediatedActivationofp38MAPK:MolecularMechanisms andBehavioralConsequences. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281 CharlesChavkin,SelenaS.Schattauer,andJamieR.Levin Arrestin-DependentLocalizationofPhosphodiesterases. . . . . . . . . . . . 293 MirandaJ.WillisandGeorgeS.Baillie ArrestinsinApoptosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 SeunghyiKook,VsevolodV.Gurevich,andEugeniaV.Gurevich MolecularMechanismsUnderlyingBeta-Arrestin-Dependent ChemotaxisandActin-CytoskeletalReorganization. . . . . . . . . . . . . . . . 341 KathrynW.McGovernandKathrynA.DeFea ArrestinsinHost–PathogenInteractions. . . . . . . . . . . . . . . . . . . . . . . . 361 StefanoMarulloandMathieuCoureuil ArrestinRegulationofSmallGTPases. . . . . . . . . . . . . . . . . . . . . . . . . . 375 RyanT.CameronandGeorgeS.Baillie GPCRsandArrestinsinAirways:ImplicationsforAsthma. . . . . . . . . 387 RaymondB.Penn,RichardA.Bond,andJuliaK.L.Walker ArrestinsasRegulatoryHubsinCancerSignallingPathways. . . . . . . . 405 Herve´ Enslen,EvelyneLima-Fernandes,andMarkG.H.Scott β-Arrestins:RegulatoryRoleandTherapeuticPotentialinOpioid andCannabinoidReceptor-MediatedAnalgesia. . . . . . . . . . . . . . . . . . 427 KirstenM.RaehalandLauraM.Bohn Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 Therapeutic Potential of Small Molecules and Engineered Proteins EugeniaV.GurevichandVsevolodV.Gurevich Contents 1 DirectActionDrugs:LigandsandInhibitors................................................. 2 2 AllostericModulators:GreaterSophistication................................................ 3 3 Protein-BasedTherapeutics:ChallengesandPotential....................................... 4 4 Signaling-BiasedArrestinsasaModel....................................................... 5 References.......................................................................................... 8 Abstract Virtually all currently used therapeutic agents are small molecules, largelybecausethedevelopmentanddeliveryofsmallmoleculedrugsisrelatively straightforward.Smallmoleculeshaveseriouslimitations:drugsofthistypecanbe fairlygoodenzymeinhibitors,receptorligands,orallostericmodulators.However, mostcellularfunctionsaremediatedbyproteininteractionswithotherproteins,and targeting protein–protein interactions by small molecules presents challenges that are unlikely to be overcome with these compounds as the only tools. Recent advances in gene delivery techniques and characterization of cell type-specific promoters open the prospect of using reengineered signaling-biased proteins as next-generationtherapeutics.Thefirststepsintargetedengineeringofproteinswith desired functional characteristicslook very promising. As quintessential scaffolds thatactstrictlyviainteractionswithotherproteinsinthecell,arrestinsrepresenta perfectmodelforthedevelopmentofthesenoveltherapeuticagentswithenormous potential:custom-designed signaling proteinswillallow ustotell thecellwhatto doandwhentodoitinawayitcannotdisobey. Keywords Drugs (cid:129) Small molecules (cid:129) Enzyme inhibitors (cid:129) Receptor ligands (cid:129) Signalingscaffolds(cid:129)Protein-basedtherapeutics E.V.Gurevich(*)(cid:129)V.V.Gurevich DepartmentofPharmacology,VanderbiltUniversity,2200PierceAvenue,Nashville, TN37232,USA e-mail:[email protected];[email protected] V.V.Gurevich(ed.),Arrestins-PharmacologyandTherapeuticPotential,Handbook 1 ofExperimentalPharmacology219,DOI10.1007/978-3-642-41199-1_1, ©Springer-VerlagBerlinHeidelberg2014
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