GPCR Introduction G protein-coupled receptors (GPCRs) are the GPCRs Super-Family largest family of transmembrane receptors and are 375 GPCR Drug Targets, 225 with Known Ligands, 150 Orphan Targets responsible for the transduction of a diverse range of extracellular signals. The range of physiological processes mediated by GPCRs makes them one GRM7 GRM8 GLUTAMATE (15) SECRETIN GRM2 FZD7 TAS1R3 FZD2 of the most important classes of proteins for drug (15) GRM4 GRM3 TAS1R1FZD1 GLP2R GIPR GRM6 GRPC6A FRIZZED/TAS2 discovery. ADHESION GLP1R GCGR GRM5 FZD3 PTHR2 GRM1 (24) LEC1 VIPR2 PTHR1 (24) TAS1R2 FZD6 LEC2 TAS2R13 CELSR2PACAP FZD8 The study of GPCRs may involve ligand binding, G CRHR2 FZD5 TAS2R16 TAS2R14 CALCRL LEC3 VIPR1 CRHR1 CASR GABBR2 FZD10 TAS2R1 TAS2R10 EMR3EMR2 CELSR3 BAI2 CALCR FZD4 TAS2R5 TAS2R3 SCTR FZD9 protein activation, internalization, and downstream ETL BAI3 GPR60 TAS2R9 CELSR1 GHRHR GABBR1 GPR59 TAS2R8 TAS2R4 TAS2R7 EMR1 BAI1 SMOH CXCR3 second messenger events. Each step of the CXCR5 CCR11 CXCR2 CD97 SSTR1 SSTR3 CCR10 CCR6 SSTR5 CXCR1 GPR111 CXCR6 pathway offers an opportunity to exploit the full SSTR2 CCR9 GPR115 SSTR4 CCR7 GPR116 GPR112 GPR8 CCRL2 GPR113 GPR7 CXC3R1CCR8 therapeutic potential of targeting GPCRs. GPR110 CCR4 HE6 NTSR2 CCR1 TM7XN1 GPR114 NMU1R GPR54 GALR1 CCBP2 GHSR GALR2 RDC1 CCR3 GPR97 NPY1R XCR1 PPYR1 NMU2R MTLR MCHR1 GALR3 ADMR NPY2R AGTR1 TACR3 UR2R MCHR2 AGTRL1 AGTR2 CCR5 TAC3RL PrRP γ GPR26 BDKRB2 CCR2 GRM7 GRM8 GLUTAMATE (15) TACR1 TACR2 GRP72 OR1A1 SALPR OLFACTORY GPR15 NPFF1 NPY5R OR1D2 (388) GPTH2 BDKRB1 FZD7 Genito Urinary System Others HCRTR2 CCKBRCCKAR β OR1G1 RECEPTORS GPR32 SECRETIN GRM2 NPFF2 ADORA1 BLTR2 and Sex Hormones GNRHRII HCRTR1 MC3D OR3A1 BLTR FPR1 TAS1R3 9% GNRHR ADORA3 δ TRHR GPR1 FZD2 3% MC5R GPR78 RE2 C5R2 FPRL2 ADORA2B α EB12 C5R1CMKLR1 (15) GRM4 TAS1R1 AVPR1A MC4R GPR119 GPR62GPR101 GRM3 FZD1 Ophthalmology GPR26 P2RY11 LGR8 FPRL1 GPR3 GPR18C3AR LGR7 MC1R RGR PTAFR GLP2R AVPR18 GPR62 GPR103 3% AVPR2 GPR6 MC2R MRGD FSHR GIPR GRM6 GRPC6A OXTR BRS3 CNR2 GPR61 LHCGR FRIZZED/TAS2 Women`s Health GPR12 SREB1 GLP1R GCGR FZD3 NMBR EDG3 CNR1 PTGER4 MRGF LGR4 TSHR GRM5 GPR50 SREB2 MRG MRGX2 ADHESION 3% MTNR1B MAS LGR6 GRPR EDG5 MTNR1A H963 PTHR2 GRM1 (24) EDG8 PTGDRSREB3 FFA1R FKSG80 Immunology EDNRA EDG6 HRH2 PTGER1 LGR5 LEC1 VIPR2 PTHR1 ETBRLP1 EDG2 GPR52 OPN4 PTGIP HM74 EDNRB P2Y12 MRGX1(24) FZD6 3% CNS ETBRLP2 GPR21 HRH3 PTGER2 F2RLA GPR92 GPR55 TAS1R2 EDG7 RRH HRH4 TBXA2R FKSG7 GPR35 EDG4 OPN3 P2Y10 MRGX3 Respiratory HTR4 PNR PTGER FKSC79 LEC2 TAS2R13 P2Y1 MRGX4 PACAP OPN1SW PTGER3 F2RL2 CELSR2 FZD8 4% 40% OPN1LW DRD5 TAS2R16 TAS2R14 DRD1 HTR6 TAR1 F2RL3 P2Y9 CRHR2 FZD5 OPN1MW TAR3 GPR87 P2Y6 GPR91 P2Y5 Gastrointestinal ADRB3 GPR58 GPR80 LEC3 CALCRL TAR5 GPR106CYSLT2CYSLT1 VIPR1 CRHR1 CASR GABBR2 TAS2R1 TAS2R10 GPR57 P2Y4 P2Y2 CELSR3 FZD10 5% TAR4 GPR17 GPR4 EMR3EMR2 OGR1 BAI2 HTR2C DRD4 CALCR TAS2R5 TAS2R3 HTR2A HTR5 G2A SCTR FZD4 GPR65 FZD9 ADRA1D HTR7 GPR60 TAS2R9 ADRA1B ETL BAI3 Metabolic Disorders ADRA1A HTR1A CELSR1 GHRHR GABBR1 GPR59 TAS2R8 7% HTR1E ADRA2A DRD2 TAS2R4 TAS2R7 HTR1F CHRM1 BAI1 SMOH CXCR3 HTR1D ADRA2C EMR1 CXCR5 Cardiovascular ADRA2B CCR11 CXCR2 7% CHRM5 RHODOPSIN SSTR3 CCR10 Oncology CHRM4 CD97 SSTR1 CCR6 CXCR1 16% (701) SSTR5 GPR111 CXCR6 SSTR2 CCR9 GPR115 SSTR4 CCR7 GPR116 GPR112 GPR8 CCRL2 GPR113 GPR7 CXC3R1CCR8 GPR110 CCR4 HE6 NTSR2 CCR1 TM7XN1 GPR114 NMU1R GPR54 GALR1 CCBP2 GHSR GALR2 RDC1 CCR3 GPCR GPR97 NPY1R XCR1 G protein-coupled receptor signaling PPYR1 NMU2R MTLR MCHR1 GALR3 ADMR NPY2R AGTR1 Classic GPCR signaling arises from heterotrimeric TACR3 UR2R MCHR2 AGTRL1 AGTR2 CCR5 TAC3RL PrRP γ GPR26 BDKRB2 CCR2 G protein dependent activation of membrane- TACR1 TACR2 GRP72 OR1A1 SALPR OLFACTORY GPR15 NPFF1 NPY5R OR1D2 (388) GPTH2 BDKRB1 delimited effectorsGenito [e.g., Urinary adenylyl System cyclaseOthers (AC), HCRTR2 CCKBRCCKAR β OR1G1 RECEPTORS GPR32 β γ NPFF2 ADORA1 BLTR2 phospholipase Cand Sexisoforms Hormones (PLC ), and ion α GNRHRII HCRTR1 MC3D OR3A1 BLTR FPR1 β 9% GOP β-arrestin GNRHR ADORA3 δ TRHR GPR1 3% MC5R GPR78 RE2 C5R2 FPRL2 channels] that generate intracellular second ADORA2B α EB12 C5R1CMKLR1 AVPR1A MC4R GPR119 GPR62GPR101 Ophthalmology GPR26 P2RY11 LGR8 FPRL1 messengers. In the current model, arrestins GPR3 GPR18C3AR LGR7 MC1R RGR 3% AVPR18 GPR62 GPR103PTAFR FSHR function as ligand-regulated scaffolds, linking ion E3 AVPR2 GPR6 MC2R MRGD AC PLCβ channel TK MAPK ligase OXTR BRS3 CNR2 GPR61 LHCGR Women`s Health GPR12 SREB1 GPCRs to nontraditional effector pathways [e.g., NMBR EDG3 CNR1 PTGER4 MRGF LGR4 TSHR GPR50 SREB2 MRG MRGX2 3% MTNR1B MAS LGR6 nonreceptor tyrosine kinases (TK), MAP kinases GRPR EDG5 MTNR1A H963 EDG8 PTGDRSREB3 FFA1R FKSG80 Immunology EDNRA EDG6 HRH2 PTGER1 LGR5 (MAPK), and E3 ubiquitin ligases]. Because ETBRLP1 EDG2 GPR52 OPN4 PTGIP HM74 EDNRB P2Y12 MRGX1 3% CNS ETBRLP2 GPR21 HRH3 PTGER2 F2RLA GPR92 GPR55 arrestin binding precludes further heterotrimeric EDG7 RRH HRH4 TBXA2R FKSG7 GPR35 G protein-dependent Arrestin-dependent EDG4 OPN3 P2Y10 MRGX3 Respiratory HTR4 PNR PTGER FKSC79 G protein coupling, these two signaling “states” P2Y1 MRGX4 signaling signaling (see page 2) OPN1SW PTGER3 F2RL2 4% 40% OPN1LW DRD5 of the receptor are mutually exclusive. DRD1 HTR6 TAR1 F2RL3 P2Y9 OPN1MW TAR3 GPR87 P2Y6 GPR91 P2Y5 Gastrointestinal GPR58 GPR80 ADRB3 TAR5 GPR106CYSLT2CYSLT1 GPR57 P2Y4 P2Y2 5% TAR4 GPR17 GPR4 HTR2C DRD4 OGR1 To order: www.abcepta.com HTR2A HTR5 G2A GPR65 ADRA1D HTR7 Email: [email protected] or [email protected] ADRA1B Metabolic Disorders ADRA1A HTR1A Tel: 858.875.19007% Fax: 858.622.0609 HTR1E ADRA2A DRD2 HTR1F CHRM1 HTR1D ADRA2C Cardiovascular ADRA2B 7% CHRM5 RHODOPSIN Oncology CHRM4 16% (701) GPCR
Allosteric interactions of GPCRs Ligand-speci c stabilization and beta-Arrestin signalling G2 G3 G4 G1 The stabilization of unique GPCR conformations β-arrestin is determined by the molecular properties of the AC PLCβ
2+ agonist, receptor and signalling proteins (in this PKA Ins(1,4,5)P3 –DAG–Ca case the different G proteins G1, G2, G3 and SRC PAP PKC ‑arrestin) at the level of the ternary complex. β RAF Stimulus input The strength of the GPCR signal imparted to the Vesicle from cell added cell by agonists is determined by the molecular MEK1 to biased signal parameters governing the direct activation of the receptor and the allosteric effect of the ligand on ERK1/ERK2 endogenous receptor affinity. This signal can then interact with other pathways in the cell and the Whole cell response total cellular response thus becomes the result of AC, adenylyl cyclase; DAG, diacylglycerol; ERK1, extracellular signal-regulated kinase 1; Ins(1,4,5) an amalgam of stimuli. P3, inositol‑1,4,5‑trisphosphate; MEK1, MAPK (mitogen-activated protein kinase)/ERK kinase 1; PAP, poly(A) polymerase; PKA, protein kinase A; PLCβ, phospholipase Cβ Under these circumstances, the stoichiometry of the GPCR signalling components in the cell can change the nature of the cellular response, making whole-cell responses cell type-dependent.
Angiotensin II Receptor Type-1 alpha1D-Adrenoceptor alpha1A-Adrenoceptor (extracellular) Antibody (extracellular) Antibody (extracellular) Antibody Cat.# AG1463 Cat.# AG1377 Cat.# AG1381
CAT. # name UNIPROT APPLICATION CAT. # name UNIPROT APPLICATION AG1383 A1 Adenosine Receptor P30542 WB,IHC,ICC AG1366 B1 Bradykinin Receptor P97583 WB,IHC AG1386 A2A Adenosine Receptor Q60613 WB,IHC AG1365 B2 Bradykinin Receptor P30411 WB,IHC AG1385 A2B Adenosine Receptor (extracellular) P29275 WB,IHC AG1300 Cannabinoid Receptor 1 (extracellular) P20272 WB,IHC AG1384 A3 Adenosine Receptor P33765 WB,IHC,ICC AG1299 Cannabinoid Receptor 2 (extracellular) P34972 WB,ICC,FC AG1381 alpha1A-Adrenoceptor (extracellular) P35348 WB,IHC AG1436 Cannabinoid Receptor 2 Q9QZN9 WB,IHC AG1378 alpha1B-Adrenoceptor (extracellular) P35368 WB,ICC,FC AG1214 Melanocortin Receptor 1 Q01726 WB,IHC,ICC AG1377 alpha1D-Adrenoceptor (extracellular) P23944 WB,IHC,FC AG1213 Melanocortin Receptor 2 (extracellular) Q01718 WB,IHC AG1376 alpha2A-Adrenoceptor (extracellular) P22909 WB AG1212 Melanocortin Receptor 3 (extracellular) P32244 WB,IHC,FC AG1375 alpha2B-Adrenoceptor (extracellular) P19328 WB,IHC AG1211 Melanocortin Receptor 4 (extracellular) P32245 WB,IHC,ICC AG1374 alpha2C-Adrenoceptor (extracellular) P22086 WB,IHC AG1210 Melanocortin Receptor 5 P41149 WB,IHC AG1463 Angiotensin II Receptor Type-1 (extracellular) P30556 WB,IHC,ICC,FC AG1298 CXCR1 (extracellular) P25024 WB,FC AG1462 Angiotensin II Receptor Type-2 (extracellular) P35351 WB,IHC,ICC AG1297 CXCR2 (extracellular) P25025 WB,FC AG1382 Angiotensin-(1-7) Mas Receptor P12526 WB,IHC AG1296 CXCR4 (extracellular) P61073 WB,IHC,FC
To order: www.abcepta.com Email: [email protected] or [email protected] Tel: 858.875.1900 Fax: 858.622.0609