SECRETIN(15)

RHODOPSIN(701)

GLUTAMATE (15)

FRIZZED/TAS2(24)ADHESION

(24)

(388)βγ

α δ

GLP2RGLP1R

GIPRGCGR

PTHR2PTHR1

GRM6

GRM4

GRM7 GRM8GRM2

GRM3

GRM5GRM1

TAS1R2

GABBR2

GABBR1

SMOH

GRPC6A

TAS1R3TAS1R1FZD1

FZD7FZD2

FZD3

FZD8

FZD6

FZD5FZD10

FZD9FZD4

TAS2R4

TAS2R1TAS2R16

TAS2R13TAS2R14TAS2R10TAS2R3TAS2R9

TAS2R8TAS2R7

TAS2R5GPR60

SSTR1 SSTR3SSTR5

SSTR2GPR8

GPR54

UR2R

GALR1GALR2GALR3MCHR1

MCHR2

GPR7SSTR4

CCR10CXCR5

CXCR3CCR11 CXCR2

CXCR1CXCR6

CCR9CCR7

CXC3R1CCRL2 CCR8

RDC1ADMR

AGTR1AGTRL1

GPR26GPR15GPTH2

AGTR2BDKRB2

BDKRB1SALPR

GPR32FPR1

FPRL2

FPRL1

GPR1C5R2

BLTR2 BLTR

C5R1CMKLR1LGR8

LGR7FSHR

LHCGRTSHR

LGR6

LGR4

LGR5

MRGX2

MRGX1

MRGX3

MRGD

MRGFMRGMAS

MRGX4

HM74

FKSG80

XCR1CCBP2

CCR4CCR1

CCR5CCR2

CCR3

CCR6

GPR59

CASRCALCR

CALCRLCRHR2

VIPR2

VIPR1BAI2

LEC1

LEC2

LEC3EMR2

EMR1CD97

GPR111

GPR115GPR116 GPR112 GPR113

GPR114 NMU1RNTSR2

GHSRMTLR

NPY5R

ADORA1ADORA3

GPR50MTNR1B

MTNR1A

GPR52GPR21

OPN4

RRHOPN3

OPN1SWOPN1LW

OPN1MWADRB3

DRD5DRD1

HTR2CHTR2A

ADRA1DADRA1B

ADRA1AHTR1EHTR1F

HTR1D

HTR7HTR5

HTR1AADRA2A

ADRA2CADRA2B

CHRM4CHRM5

CHRM1DRD2

DRD4TAR4

TAR5TAR3

PTGER1 PTGER2PTGERTBXA2RPTGER3

HTR4

HTR6 TAR1

HRH3

HRH2

HRH4PNR

GPR78

OR1A1OR1D2OR1G1OR3A1

OLFACTORYRECEPTORS

GPR119 GPR26

GPR62GPR61

SREB1SREB2

H963FFA1R

F2RLA

F2RL

2F2

RL3

GPR1

06GPR8

7CY

SLT2

CYSL

T1GP

R17

GPR6

5G2

AGP

R4OG

R1P2Y4P2Y2

P2Y6 GPR80GPR91P2Y5

P2Y9

P2Y1P2Y10

FKSC79GPR92GPR35

GPR55

RGRGPR103PTAFR

GPR18

C3ARP2RY11

GPR62

EB12 GPR101

RE2TRHR

PTGIPP2Y12FKSG7

PTGER4

PTGDRSREB3

GPR57GPR58

MC3DMC5R

ADORA2BMC4R

MC1RMC2R

GPR12

GPR3

CNR2CNR1EDG3

EDG5EDG8 EDG6

EDG2

EDG7

EDNRA

GRPR

ETBRLP1

ETBRLP2 EDNRB

EDG4

GPR6

CCKARCCKBRHCRTR2HCRTR1

NPFF2GNRHRII

GNRHR

AVPR1A

AVPR18OXTR

AVPR2BRS3

NMBR

NMU2RNPY1RGPR97 PPYR1NPY2R

PrRPTACR3

TACR1NPFF1

TACR2 GRP72TAC3RL

GPR110TM7XN1 HE6

EMR3

ETL

BAI1

BAI3SCTR

GHRHR

PACAPCELSR2

CELSR3

CELSR1

CRHR1

Others 9%

Genito Urinary Systemand Sex Hormones

3%

Ophthalmology3%

Women`s Health3%

Immunology3%

Respiratory4%

Gastrointestinal5%

Metabolic Disorders7%

Cardiovascular7% Oncology

16%

CNS40%

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and are responsible for the transduction of a diverse range of extracellular signals. The range of physiological processes mediated by GPCRs makes them one of the most important classes of proteins for drug discovery.

The study of GPCRs may involve ligand binding, G protein activation, internalization, and downstream second messenger events. Each step of the pathway offers an opportunity to exploit the full therapeutic potential of targeting GPCRs.

Introduction

G protein-dependentsignaling

AC PLCβ ion channel

Arrestin-dependentsignaling (see page 2)

TK MAPK E3ligase

GOPα

β γ

β-arrestin

GPCR

Classic GPCR signaling arises from heterotrimeric G protein dependent activation of membrane-delimited effectors [e.g., adenylyl cyclase (AC), phospholipase C isoforms (PLCβ), and ion channels] that generate intracellular second messengers. In the current model, arrestins function as ligand-regulated scaffolds, linking GPCRs to nontraditional effector pathways [e.g., nonreceptor tyrosine kinases (TK), MAP kinases (MAPK), and E3 ubiquitin ligases]. Because arrestin binding precludes further heterotrimeric G protein coupling, these two signaling “states” of the receptor are mutually exclusive.

G protein-coupled receptor signaling

SECRETIN(15)

RHODOPSIN(701)

GLUTAMATE (15)

FRIZZED/TAS2(24)ADHESION

(24)

(388)βγ

α δ

GLP2RGLP1R

GIPRGCGR

PTHR2PTHR1

GRM6

GRM4

GRM7 GRM8GRM2

GRM3

GRM5GRM1

TAS1R2

GABBR2

GABBR1

SMOH

GRPC6A

TAS1R3TAS1R1FZD1

FZD7FZD2

FZD3

FZD8

FZD6

FZD5FZD10

FZD9FZD4

TAS2R4

TAS2R1TAS2R16

TAS2R13TAS2R14TAS2R10TAS2R3TAS2R9

TAS2R8TAS2R7

TAS2R5GPR60

SSTR1 SSTR3SSTR5

SSTR2GPR8

GPR54

UR2R

GALR1GALR2GALR3MCHR1

MCHR2

GPR7SSTR4

CCR10CXCR5

CXCR3CCR11 CXCR2

CXCR1CXCR6

CCR9CCR7

CXC3R1CCRL2 CCR8

RDC1ADMR

AGTR1AGTRL1

GPR26GPR15GPTH2

AGTR2BDKRB2

BDKRB1SALPR

GPR32FPR1

FPRL2

FPRL1

GPR1C5R2

BLTR2 BLTR

C5R1CMKLR1LGR8

LGR7FSHR

LHCGRTSHR

LGR6

LGR4

LGR5

MRGX2

MRGX1

MRGX3

MRGD

MRGFMRGMAS

MRGX4

HM74

FKSG80

XCR1CCBP2

CCR4CCR1

CCR5CCR2

CCR3

CCR6

GPR59

CASRCALCR

CALCRLCRHR2

VIPR2

VIPR1BAI2

LEC1

LEC2

LEC3EMR2

EMR1CD97

GPR111

GPR115GPR116 GPR112 GPR113

GPR114 NMU1RNTSR2

GHSRMTLR

NPY5R

ADORA1ADORA3

GPR50MTNR1B

MTNR1A

GPR52GPR21

OPN4

RRHOPN3

OPN1SWOPN1LW

OPN1MWADRB3

DRD5DRD1

HTR2CHTR2A

ADRA1DADRA1B

ADRA1AHTR1EHTR1F

HTR1D

HTR7HTR5

HTR1AADRA2A

ADRA2CADRA2B

CHRM4CHRM5

CHRM1DRD2

DRD4TAR4

TAR5TAR3

PTGER1 PTGER2PTGERTBXA2RPTGER3

HTR4

HTR6 TAR1

HRH3

HRH2

HRH4PNR

GPR78

OR1A1OR1D2OR1G1OR3A1

OLFACTORYRECEPTORS

GPR119 GPR26

GPR62GPR61

SREB1SREB2

H963FFA1R

F2RLA

F2RL

2F2

RL3

GPR1

06GPR8

7CY

SLT2

CYSL

T1GP

R17

GPR6

5G2

AGP

R4OG

R1P2Y4P2Y2

P2Y6 GPR80GPR91P2Y5

P2Y9

P2Y1P2Y10

FKSC79GPR92GPR35

GPR55

RGRGPR103PTAFR

GPR18

C3ARP2RY11

GPR62

EB12 GPR101

RE2TRHR

PTGIPP2Y12FKSG7

PTGER4

PTGDRSREB3

GPR57GPR58

MC3DMC5R

ADORA2BMC4R

MC1RMC2R

GPR12

GPR3

CNR2CNR1EDG3

EDG5EDG8 EDG6

EDG2

EDG7

EDNRA

GRPR

ETBRLP1

ETBRLP2 EDNRB

EDG4

GPR6

CCKARCCKBRHCRTR2HCRTR1

NPFF2GNRHRII

GNRHR

AVPR1A

AVPR18OXTR

AVPR2BRS3

NMBR

NMU2RNPY1RGPR97 PPYR1NPY2R

PrRPTACR3

TACR1NPFF1

TACR2 GRP72TAC3RL

GPR110TM7XN1 HE6

EMR3

ETL

BAI1

BAI3SCTR

GHRHR

PACAPCELSR2

CELSR3

CELSR1

CRHR1

Others 9%

Genito Urinary Systemand Sex Hormones

3%

Ophthalmology3%

Women`s Health3%

Immunology3%

Respiratory4%

Gastrointestinal5%

Metabolic Disorders7%

Cardiovascular7% Oncology

16%

CNS40%

GPCRs Super-Family 375 GPCR Drug Targets, 225 with Known Ligands, 150 Orphan Targets

GPCR

To order: www.stratech.co.uk/abceptaEmail: orders@stratech.co.uk

CAT. # nAme UnIPROT APPLICATIOn

AG1383 A1 Adenosine Receptor P30542 WB,IHC,ICC

AG1386 A2A Adenosine Receptor Q60613 WB,IHC

AG1385 A2B Adenosine Receptor (extracellular) P29275 WB,IHC

AG1384 A3 Adenosine Receptor P33765 WB,IHC,ICC

AG1381 alpha1A-Adrenoceptor (extracellular) P35348 WB,IHC

AG1378 alpha1B-Adrenoceptor (extracellular) P35368 WB,ICC,FC

AG1377 alpha1D-Adrenoceptor (extracellular) P23944 WB,IHC,FC

AG1376 alpha2A-Adrenoceptor (extracellular) P22909 WB

AG1375 alpha2B-Adrenoceptor (extracellular) P19328 WB,IHC

AG1374 alpha2C-Adrenoceptor (extracellular) P22086 WB,IHC

AG1463 Angiotensin II Receptor Type-1 (extracellular) P30556 WB,IHC,ICC,FC

AG1462 Angiotensin II Receptor Type-2 (extracellular) P35351 WB,IHC,ICC

AG1382 Angiotensin-(1-7) Mas Receptor P12526 WB,IHC

CAT. # nAme UnIPROT APPLICATIOn

AG1366 B1 Bradykinin Receptor P97583 WB,IHC

AG1365 B2 Bradykinin Receptor P30411 WB,IHC

AG1300 Cannabinoid Receptor 1 (extracellular) P20272 WB,IHC

AG1299 Cannabinoid Receptor 2 (extracellular) P34972 WB,ICC,FC

AG1436 Cannabinoid Receptor 2 Q9QZN9 WB,IHC

AG1214 Melanocortin Receptor 1 Q01726 WB,IHC,ICC

AG1213 Melanocortin Receptor 2 (extracellular) Q01718 WB,IHC

AG1212 Melanocortin Receptor 3 (extracellular) P32244 WB,IHC,FC

AG1211 Melanocortin Receptor 4 (extracellular) P32245 WB,IHC,ICC

AG1210 Melanocortin Receptor 5 P41149 WB,IHC

AG1298 CXCR1 (extracellular) P25024 WB,FC

AG1297 CXCR2 (extracellular) P25025 WB,FC

AG1296 CXCR4 (extracellular) P61073 WB,IHC,FC

The stabilization of unique GPCR conformations is determined by the molecular properties of the agonist, receptor and signalling proteins (in this case the different G proteins G1, G2, G3 and β-arrestin) at the level of the ternary complex.

The strength of the GPCR signal imparted to the cell by agonists is determined by the molecular parameters governing the direct activation of the receptor and the allosteric effect of the ligand on endogenous receptor affinity. This signal can then interact with other pathways in the cell and the total cellular response thus becomes the result of an amalgam of stimuli.

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.

Allosteric interactions of GPCRsand beta-Arrestin signalling

AC, adenylyl cyclase; DAG, diacylglycerol; ERK1, extracellular signal-regulated kinase 1; Ins(1,4,5)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

alpha1A-Adrenoceptor (extracellular) AntibodyCat.# AG1381

alpha1D-Adrenoceptor (extracellular) AntibodyCat.# AG1377

Angiotensin II Receptor Type-1 (extracellular) Antibody Cat.# AG1463

ERK1/ERK2

Ins(1,4,5)P32+–DAG–Ca

Whole cell response

Stimulus inputfrom cell addedto biased signal

Ligand-speci�c stabilization

Vesicle

PKC

PKA

RAF

AC PLCβ

SRC PAP

MEK1

G4

G1

G3G2

β-arrestin

GPCR

To order: www.stratech.co.uk/abceptaEmail: orders@stratech.co.uk