Signal Transductionthreetypes of receptors1.G-protein-linked receptor2.lonotropicreceptor3.Enzyme-linkedreceptor
Signal Transduction three types of receptors 1. G-protein-linked receptor 2. Ionotropic receptor 3. Enzyme-linked receptor
G-proteinCoupledReceptorsG-Proteincoupledreceptors,alsoExtracellular sideknownas7-transmembraneorserpentinereceptorsbecause7a-helices passthroughtheCarbohydratemembrane,arethelargestfamilyNoftransducerproteins,andthelargestfamilyofproteinsknownThehumangenomecodesforatleast90G-proteins.LigandsfortheGPCRrangefromphotonsthroughsmalltransmitterstoproteinsignalingmoleculesoftheimmunesystemGPCR'saretargetsfor40-50%ofmedicinaldrugsCytosolic side
G-protein Coupled Receptors G-Protein coupled receptors, also known as 7-transmembrane or serpentine receptors because 7 ahelices pass through the membrane, are the largest family of transducer proteins, and the largest family of proteins known. The human genome codes for at least 90 G-proteins. Ligands for the GPCR range from photons through small transmitters to protein signaling molecules of the immune system. GPCR’s are targets for 40-50% of medicinal drugs
Signal TransductionThroughG-protein-linkedReceptorGprotein-coupledreceptorsAnonG-PROTEINCytoplasmVOAOSIONAINSIDACPLCAdenylylCyclasePhospholipaseCCAMP[Ca2+]PKCtwoprincipalpathways:-cAMP.signalpathwayTERH---PhosphatidylinositolpathwayPKA@ELSEVIER,INC,-ELSEVIERIMAGES.COM
Signal Transduction Through G-protein-linked Receptor Adenylyl Cyclase Phospholipase C two principal pathways: - cAMP signal pathway - Phosphatidylinositol pathway
AdrenalineCAdrenergicAdenylytreceptorCyclaseactivationGDPGTFAdenylylCyclaseATI(AC)PathwayCyclicAMP&PKACYTOPLASMCAMPNUCLEUSTranscriptionActivatedtargetgeneregulatorDNADOMOTranscriptionRNAnexampleof signaltransductioncascadeinvolvingcyclicAMPThebinding of adrenalinetoanadrenergicreceptor initiates a cascadeofreactions insidethe cell.The signaltransductioncascadebeginswhenadenylylcyclase,amembrane-boundenzyme,becomesactivatedbyG-protein moleculesassociatedwith theadrenergic receptor.Adenylyl cyclase creates multiple cyclicAMpmolecules,whichfanoutand activateproteinkinases(PkA,inthisexample).Proteinkinasescan enter thenucleusandaffecttranscription
Adenylyl Cyclase (AC) Pathway & cAMP
PhospholipaseC(PLC)PathwayExtracellularTheDualPLC/IP3/DAGpathway:PLCcleavesthephospholipidLSignalingPathwayGPLRphosphatidylinositol4,5-bisphosphate(PiP2)yieldingdiacylglycerol(DAG)andinositol1,4,5-triphosphate(IP3).DAGDAGremainsboundtothemembrane,andIP3isreleasedasaPIP2PKCPLCBsolublestructureintothecytosol.IPathendiffusesthroughthecytosolto bindto IPreceptors,particularcalcium channels inCytoplasmtheendoplasmicreticulum(ER).ThesechannelsarespecifictoIP3CaBPscalciumandonlyallowthepassageofcalciumto movethrough.ERThiscausesthecytosolicconcentrationofCalciumto increase,IP3Rcausinga cascade of intracellularchanges and activity.[43] InCaMaddition,calciumandDAGtogetherworkstoactivatePKC,whichgoesontophosphorylateothermolecules,leadingtoalteredcellularactivity
Phospholipase C (PLC) Pathway