Gastrin-CREB signaling via PKC and MAPK (Homo sapiens)

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2, 8, 3321, 26, 29, 35, 372175, 1423, 24274162228136, 171, 411534181011, 311925, 30NPSNPSR Orexin 2 receptorOrexin B G-protein alpha Carboxylate ligands of FFAR2 FP receptorPGF2-alpha Orexin 1 receptorOrexin A Prokineticin PAF receptorPAF Substance K receptorNeurokinin A peptide Carboxylate ligands of FFAR3 Bradykinin receptor Carboxylate ligands of FFAR3 GRB2SOS1 PLC betaG alpha GastrinCCKBR FFAR3Carboxylate ligands Neuromedin-SNeuromedin-U receptor 2 Neuropeptide FF receptor 5-HT2 receptorSerotonin P2RY1ADP GastrinCCKBR G-protein alpha p21 RAS HB-EGFp-6Y-EGFR G-protein alpha Melanin-concentrating hormone receptors Proteinase-activated receptors Alpha-1 adrenoceptor G-protein alpha CHRM1, 3, 5 P2RY10LPA Vasopressin receptor type 1 Motilin receptorMotilin Type 1 angiotensin II receptorAngiotensin II TRHTRHR Cysteinyl leukotriene receptorsCysteinyl leukotrienes Heterotrimeric G-protein Gq/11 CASRCalcium P2RY9LPA G-protein alpha G-protein alpha G-protein beta-gamma complex MetastinKiSS1R Neuropeptide FF receptor G-protein alpha Group I Metabotropic glutamate receptorsGlu Bombesin-like peptide EndothelinEndothelin receptor G-protein alpha LTB4 receptorsLTB4 Neuromedin-SNeuromedin-U receptor 2 Melanospinphoton Prokineticin Carboxylate ligands of FFAR2 Catecholamine FPRL1 ligands CCKCholecystokinin receptors Neuromedin-U receptors nucleoplasmNeurotensin receptor FPRL1FPRL1 ligands P2RY9LPA XC1 ligands Bradykinin receptorBradykinin LPA-binding EDG receptors LPA CCKCholecystokinin receptors Cysteinyl leukotriene receptors 5-HT2 receptor Prokineticin receptorsprokineticin GlucagonGCGR Bombesin-like receptorbombesin-like peptide Motilin receptorMotilin NeurotensinNeurotensin receptor Neuromedin-UNeuromedin receptors Cholecystokinin receptors Bradykinin receptor G-protein alpha P2RY11 ATP Heterotrimeric G-protein Gq/11 P2RY2ATP Chemokine XC receptor 1 XC1 ligands LPA-binding EDG receptors Group I Metabotropic glutamate receptors Acyl ghrelinGHSR Urotensin 2, 2B CHRM1, 3, 5 FPRL1FPRL1 ligands Endothelin receptor GPRC6A ligands Vasopressin receptor type 1AVP p21 RASGDP Alpha-1 adrenoceptorCatecholamine MetastinKiSS1R M1/M3/M5acetylcholine TP receptorThromboxane A2 5-HT2 receptorSerotonin LPA-binding EDG receptors LPA pH sensing receptorsH+ Endothelin LTB4 receptorsLTB4 FFAR3Carboxylate ligands EndothelinEndothelin receptor GPRC6A receptorGPRC6A ligands Prokineticin receptors GPRC6A ligands Cysteinyl leukotriene receptors 5-HT2 receptor G-protein alpha GnRH receptor G-protein alpha Prokineticin receptors Prokineticin receptorsprokineticin Acyl ghrelinGHSR UTS2RUrotensin 2, 2B G-protein beta-gamma complex LTB4 receptors MCHMelanin-concentrating hormone receptors GPR17UDP Endothelin Acyl Ghrelin FPRL1 ligands NeurotensinNeurotensin receptor OxytocinOxytocin receptor LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq Heterotrimeric G-protein Gq G-protein alpha Melanin-concentrating hormone receptors Activated thrombin FP receptorPGF2-alpha G-protein alpha Cholecystokinin receptors Urotensin 2, 2B Acyl Ghrelin Basic L-amino acids QRFP receptorQRFP GNRH ligands Neurotensin receptor GRB2SOS1HB-EGFp-6Y-EGFR GnRH receptor HB-EGFp-6Y-EGFR dimer Ligands of FFAR1 G-protein alpha MCHMelanin-concentrating hormone receptors Chemokine XC receptor 1 XC1 ligands Cysteinyl leukotrienes Substance P receptorSubstance P peptide Orexin 1 receptorOrexin A P2RY1ADP G-protein alpha XC1 ligands p21 RASGTP Substance K receptorNeurokinin A peptide G-protein alpha GnRH receptorGNRH ligands G-protein alpha LTB4 receptors HRH1Histamine Bombesin-like receptorbombesin-like peptide FFAR1fatty acid Proteinase-activated receptors Orexin 2 receptorOrexin B G-protein alpha PAF receptorPAF TRH P2RY5LPA PLC-beta FFAR2Carboxylate ligands OxytocinOxytocin receptor EP1 receptorPGE2 p21 RAS UTS2RUrotensin 2, 2B QRFP receptorQRFP G-protein alpha G-protein alpha PI3K alpha G-protein beta-gamma complex Vasopressin receptor type 1 Bombesin-like peptide Neuromedin-UNeuromedin receptors cytosolBasic L-amino acids G-protein alpha Melanospinphoton GlucagonGCGR Substance P receptorSubstance P peptide P2RY6UDP G-protein beta-gamma complex Protein Kinase C, alpha type DAG LigandGPCR complexes that activate Gq/11 P2RY11 ATP pH sensing receptors Endothelin receptor G-protein alpha M1/M3/M5acetylcholine G-protein alpha Neuromedin K receptorNeurokinin B peptide Ligands of FFAR1 TRIO family RhoGEFs PI3K alpha NPSNPSR FFAR2Carboxylate ligands HB-EGFp-6Y-EGFR HB-EGFp-6Y-EGFR dimer TP receptorThromboxane A2 Group I Metabotropic glutamate receptorsGlu Cysteinyl leukotriene receptorsCysteinyl leukotrienes GRB2SOS1 Alpha-1 adrenoceptor Cysteinyl leukotrienes Catecholamine GPR17UDP Neuropeptide FF receptorNeuropeptide FF CASRCalcium Group I Metabotropic glutamate receptors G-protein alpha Activated thrombin Neuromedin-U receptors GNRH ligands GPRC6A receptorGPRC6A ligands Type 1 angiotensin II receptorAngiotensin II P2RY6UDP pH sensing receptorsH+ FFAR1fatty acid P2RY2ATP Neuromedin K receptorNeurokinin B peptide TRHTRHR Vasopressin receptor type 1AVP pH sensing receptors Neuropeptide FF receptorNeuropeptide FF ThrombinProteinase-activated receptors Bradykinin receptorBradykinin LPA-binding EDG receptors TRH GastrinCCKBR P2RY10LPA P2RY5LPA LigandGPCR complexes that activate Gq/11 GnRH receptorGNRH ligands LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq HRH1Histamine ThrombinProteinase-activated receptors Alpha-1 adrenoceptorCatecholamine EP1 receptorPGE2 GNA15 GDP Hist LTC4 PIK3CA AVPR1B P2RY6 GHSR HTR2B GTP PI3K alphap-ERK1/2/5GDP NTSADP CASR LPAR1 AGTR1 P2RY6 MCHR2 EDNRA NMBTRIO family RhoGEFsGTPDecS-GHRL-1thrombin light chain UDP LPAR5 O-octanoyl-L-serine-GHRL-1GPR4 NAd PRKCA HCRTR2 DecS-GHRL-1CCKAR OXTGRM5 PAF GNA14 PLC-betaGRM1 NMUR1 ATPNMUMT-RNR2GNAQ EDN2LPAR5 CYSLTR2 CHRM5 GNA11 CHRM1 HBEGFTRHR NMUGNA15 PROKR1 ARHGEF25 NMBPROKR2 PGE2 GPR65 GNA11 OLEA PLC betaG alpha TBXA2RMLNAVPADRA1B GRK5GNA11 QRFPR DDCX XCR1 TRHADPGNA11 HTR2A thrombin light chain NTSR2 GNRH1CH3COO- NAd TRHKISS1R GNAQ LPAR4 BDKRB2 OXTR TACR2 FPR2 GPR68 HB-EGFp-6Y-EGFR dimerSubstance P peptide Pentadecanoic acid TAC3GPRC6A CCL23-2 GNA11 G-protein alpha ATP LTC4 GASTGTP PRKCALTE4 EDN3Ca2+ Pentadecanoic acid ADPG-protein alpha GRB2-1 L-Lys CHRM5 ANXA1 HCRTR1 GNAQ P2RY10 HBEGFHCRTHCRTR2 MLNR AVPR1B GDP MT-RNR2GNAQ HXA GNAQ HRASAGTGNRH2OPN4 Valerate TXA2 FFAR2 GNA15 GNA14 UTS2GNA11 CCL23-2 MLNADRBK1thrombin heavy chain TRHMCHR2 LTD4 NPSR1 GTP HCRTHTR2A O-octanoyl-L-serine-GHRL-1GHSR LPAR3 ADP DAG NTSR1 Glu FFAR3 PROK1 GRPNeurokinin A peptide OLEA Neurokinin A peptide p-6Y-EGFR NTSGNRHR2Bradykinin G-protein alpha F2RL3GNRH2MLNR GNA15 GDPKISS1R APPCREB1PROK1 CCK PLCB4 GNRH1GTPF2RL2PMCHSOS1 TRHHCRTR1 HXA LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq GRPKRASGRB2SOS1CCKBR GNA15 GNA15 AcCho PROK2 GCGR UDP NRAS LTB4 LTD4 HBEGFPGF2a TXA2 PALM L-Arg TRIO TRHP2RY10 TRHR XCL2 F2REGFRRGZ DecS-GHRL-1KISS1EDNRA G-protein alpha TACR3 CYSLTR2 FPR2 F2RGNA14 PROK2 AcCho LTB4R2 LPAR1 PALM GPR132 DAGUTS2Effects of PIP2 hydrolysisEtCOO- or C2H5COO- ADR GASTGNA15 UTS2BEDN1LPAR2 PTAFR APPQRFPR FFAR1 ADRBK1LPAR6 HRH1 HCOOH L-Lys Valerate PAF LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq TRHATPGDP L-Arg CH3COO- CCKAR NMUR2 thrombin heavy chain NMUR2 G-protein beta-gamma complexGNAQ NPFFR1 HCRTGPRC6A Ribosomal protein S6 kinaseO-octanoyl-L-serine-GHRL-1LTB4R NPFFR1 CCK PGF2a PTGFR HTR2CTRHPhospho-Ribosomal protein S6 kinaseINPSGNA11 G-protein alpha AVPR1A NPFFLTE4 LPAR6 CHRM3 PGE2 GASTTACR3 ATP NRAS P2RY11 GRM1 CHRM1 ADRA1A XCL2 BDKRB1 PTAFR UTS2BHCRTP2RY2 MCHR1 Glucagon SAA1PROKR2 CHRM3 GNA15 GastrinCCKBRADR P2RY11 GTP KRASGRB2SOS1HB-EGFp-6Y-EGFRGPCRs that activate Gq/11TACR2 TRHSubstance P peptide F2RL1BUT GNA14 PTGER1 MCHR1 RGS proteins active for G alpha SOS1 TAC3FFAR2 ADRA1A Heterotrimeric G-protein Gq/11 Ca2+ GPR17 HBEGFGNA15 GNA11 AVPADRA1D GPR65 Ligands of GPCRs that activate Gq/11BDKRB1 GNRHR GPR17 5HT LPA GNA11 PROKR1 TRHFFAR1 GNA14 GCGR GRB2-1 GTP TACR1 GDPGNA15 Hist NPFFR2 CYSLTR1 AGTHBEGFTACR1 NMSPIGPR132 NPFFR2 XCL1 GNA14 HTR2B LigandGPCR complexes that activate Gq/11EDN2GNA14 GNRHR2GTP DecS-GHRL-1LTB4R2 CCKBRMMP3p-S133-CREB1UTS2R PLCB2 OXTNMUR1 HRASGlucagon LTB4 LPAR2 GNA14 GRK5 p-6Y-EGFR NPSR1 TRHEDN3G-protein alpha PIK3CA GRM5 PTGFR SAA1PLCB3NMSGNA11 GNAQ EDNRB XCR1 F2RL1GPR4 LXA4 LPAR4 5HT FFAR3 GNA14 CASR LPA NTSR2 P2RY1 LPAR3 BDKRB2 AGTR1 HCOOH L-Orn PTGER1 H+ RGZ p21 RASGDPCCKBR GNRHR O-octanoyl-L-serine-GHRL-1DDCX EtCOO- or C2H5COO- LTB4R ADRA1B GTP ADRA1D TBXA2RQRFPGPR68 P2RY1 TRHXCL1 GNAQ GTP CYSLTR1 H+ LXA4 P2RY2 KISS1EDNRB TRHG-protein alpha Glu OPN4 NTSR1 GNAQ Bradykinin NPFFF2RL3HTR2CRAF/MAP kinase cascadeL-Orn PLCB1 GASTAVPR1A GNAQ UTS2R PMCHGNA14 BUT Protein Kinase C, alpha type DAGF2RL2QRFPOXTR HBEGFKALRN CCKBR ANXA1 HRH1 EDN1p21 RASGTPNPS9, 3620, 39, 409, 3612, 389, 369, 363, 32


Description

Gastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic factor for gastrointestinal epithelial cells. Gastrin has two biologically active peptide forms, G34 and G17.Gastrin gene expression is upregulated in both a number of pre-malignant conditions and in established cancer through a variety of mechanisms. Depending on the tissue where it is expressed and the level of expression, differential processing of the polypeptide product leads to the production of different biologically active peptides. In turn, acting through the classical gastrin cholecystokinin B receptor CCK-BR, its isoforms and alternative receptors, these peptides trigger signalling pathways which influence the expression of downstream genes that affect cell survival, angiogenesis and invasion (Wank 1995, de Weerth et al. 1999, Grabowska & Watson 2007) Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=881907

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Bibliography

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History

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CompareRevisionActionTimeUserComment
129720view01:33, 22 May 2024EweitzModified title
116412view09:06, 7 May 2021EweitzModified title
115053view16:59, 25 January 2021ReactomeTeamReactome version 75
113497view11:57, 2 November 2020ReactomeTeamReactome version 74
112697view16:09, 9 October 2020ReactomeTeamReactome version 73
101614view11:48, 1 November 2018ReactomeTeamreactome version 66
101150view21:34, 31 October 2018ReactomeTeamreactome version 65
100678view20:07, 31 October 2018ReactomeTeamreactome version 64
100228view16:52, 31 October 2018ReactomeTeamreactome version 63
99779view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99335view12:47, 31 October 2018ReactomeTeamreactome version 62
93801view13:37, 16 August 2017ReactomeTeamreactome version 61
93339view11:20, 9 August 2017ReactomeTeamreactome version 61
87453view14:00, 22 July 2016MkutmonOntology Term : 'signaling pathway' added !
86425view09:17, 11 July 2016ReactomeTeamreactome version 56
83266view10:35, 18 November 2015ReactomeTeamVersion54
81375view12:54, 21 August 2015ReactomeTeamVersion53
76844view08:07, 17 July 2014ReactomeTeamFixed remaining interactions
76548view11:53, 16 July 2014ReactomeTeamFixed remaining interactions
75881view09:53, 11 June 2014ReactomeTeamRe-fixing comment source
75581view10:41, 10 June 2014ReactomeTeamReactome 48 Update
74936view13:46, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74580view08:37, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
5HT MetaboliteCHEBI:28790 (ChEBI)
ADP MetaboliteCHEBI:16761 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ADR MetaboliteCHEBI:28918 (ChEBI)
ADRA1A ProteinP35348 (Uniprot-TrEMBL)
ADRA1B ProteinP35368 (Uniprot-TrEMBL)
ADRA1D ProteinP25100 (Uniprot-TrEMBL)
ADRBK1ProteinP25098 (Uniprot-TrEMBL)
AGTProteinP01019 (Uniprot-TrEMBL)
AGTR1 ProteinP30556 (Uniprot-TrEMBL)
ANXA1 ProteinP04083 (Uniprot-TrEMBL)
APPProteinP05067 (Uniprot-TrEMBL)
ARHGEF25 ProteinQ86VW2 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
AVPProteinP01185 (Uniprot-TrEMBL)
AVPR1A ProteinP37288 (Uniprot-TrEMBL)
AVPR1B ProteinP47901 (Uniprot-TrEMBL)
AcCho MetaboliteCHEBI:15355 (ChEBI)
BDKRB1 ProteinP46663 (Uniprot-TrEMBL)
BDKRB2 ProteinP30411 (Uniprot-TrEMBL)
BUT MetaboliteCHEBI:30772 (ChEBI)
Bradykinin ProteinP01042 (Uniprot-TrEMBL)
CASR ProteinP41180 (Uniprot-TrEMBL)
CCK ProteinP06307 (Uniprot-TrEMBL)
CCKAR ProteinP32238 (Uniprot-TrEMBL)
CCKBR ProteinP32239 (Uniprot-TrEMBL)
CCKBRProteinP32239 (Uniprot-TrEMBL)
CCL23-2 ProteinP55773-2 (Uniprot-TrEMBL)
CH3COO- MetaboliteCHEBI:15366 (ChEBI)
CHRM1 ProteinP11229 (Uniprot-TrEMBL)
CHRM3 ProteinP20309 (Uniprot-TrEMBL)
CHRM5 ProteinP08912 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
CYSLTR1 ProteinQ9Y271 (Uniprot-TrEMBL)
CYSLTR2 ProteinQ9NS75 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
DDCX MetaboliteCHEBI:30805 (ChEBI)
DecS-GHRL-1ProteinQ9UBU3-1 (Uniprot-TrEMBL)
EDN1ProteinP05305 (Uniprot-TrEMBL)
EDN2ProteinP20800 (Uniprot-TrEMBL)
EDN3ProteinP14138 (Uniprot-TrEMBL)
EDNRA ProteinP25101 (Uniprot-TrEMBL)
EDNRB ProteinP24530 (Uniprot-TrEMBL)
EGFRProteinP00533 (Uniprot-TrEMBL)
Effects of PIP2 hydrolysisPathwayREACT_2202 (Reactome) Hydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by phospholipase C (PLC) produces diacylglycerol (DAG) and inositol triphosphate (IP3). Both are potent second messengers. IP3 diffuses into the cytosol, but as DAG is a hydrophobic lipid it remains within the plasma membrane. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, while DAG activates the conventional and unconventional protein kinase C (PKC) isoforms, facilitating the translocation of PKC from the cytosol to the plasma membrane. The effects of DAG are mimicked by tumor-promoting phorbol esters. DAG is also a precursor for the biosynthesis of prostaglandins, the endocannabinoid 2-arachidonoylglycerol and an activator of a subfamily of TRP-C (Transient Receptor Potential Canonical) cation channels 3, 6, and 7.
EtCOO- or C2H5COO- MetaboliteCHEBI:30768 (ChEBI)
F2RL1ProteinP55085 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RL2ProteinO00254 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RL3ProteinQ96RI0 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RProteinP25116 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
FFAR1 ProteinO14842 (Uniprot-TrEMBL)
FFAR2 ProteinO15552 (Uniprot-TrEMBL)
FFAR3 ProteinO14843 (Uniprot-TrEMBL)
FPR2 ProteinP25090 (Uniprot-TrEMBL)
G-protein alpha ProteinREACT_18229 (Reactome)
G-protein alpha ComplexREACT_19587 (Reactome)
G-protein alpha ComplexREACT_19592 (Reactome)
G-protein alpha ComplexREACT_19870 (Reactome)
G-protein alpha ComplexREACT_20202 (Reactome)
G-protein alpha ComplexREACT_3769 (Reactome)
G-protein alpha ComplexREACT_5863 (Reactome)
G-protein beta-gamma complexComplexREACT_15674 (Reactome)
GASTProteinP01350 (Uniprot-TrEMBL)
GCGR ProteinP47871 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GHSR ProteinQ92847 (Uniprot-TrEMBL)
GNA11 ProteinP29992 (Uniprot-TrEMBL)
GNA14 ProteinO95837 (Uniprot-TrEMBL)
GNA15 ProteinP30679 (Uniprot-TrEMBL)
GNAQ ProteinP50148 (Uniprot-TrEMBL)
GNRH1ProteinP01148 (Uniprot-TrEMBL)
GNRH2ProteinO43555 (Uniprot-TrEMBL)
GNRHR ProteinP30968 (Uniprot-TrEMBL)
GNRHR2ProteinQ96P88 (Uniprot-TrEMBL)
GPCRs that activate Gq/11ProteinREACT_22567 (Reactome)
GPR132 ProteinQ9UNW8 (Uniprot-TrEMBL)
GPR17 ProteinQ13304 (Uniprot-TrEMBL)
GPR4 ProteinP46093 (Uniprot-TrEMBL)
GPR65 ProteinQ8IYL9 (Uniprot-TrEMBL)
GPR68 ProteinQ15743 (Uniprot-TrEMBL)
GPRC6A ProteinQ5T6X5 (Uniprot-TrEMBL)
GRB2

SOS1 HB-EGF

p-6Y-EGFR		ComplexREACT_124650 (Reactome)
GRB2 SOS1ComplexREACT_4435 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRK5 ProteinP34947 (Uniprot-TrEMBL)
GRK5ProteinP34947 (Uniprot-TrEMBL)
GRM1 ProteinQ13255 (Uniprot-TrEMBL)
GRM5 ProteinP41594 (Uniprot-TrEMBL)
GRPProteinP07492 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Gastrin CCKBRComplexREACT_24587 (Reactome)
Glu MetaboliteCHEBI:16015 (ChEBI)
Glucagon ProteinP01275 (Uniprot-TrEMBL)
H+ MetaboliteCHEBI:15378 (ChEBI)
HB-EGF p-6Y-EGFR dimerComplexREACT_123414 (Reactome)
HBEGFProteinQ99075 (Uniprot-TrEMBL)
HCOOH MetaboliteCHEBI:30751 (ChEBI)
HCRTProteinO43612 (Uniprot-TrEMBL)
HCRTR1 ProteinO43613 (Uniprot-TrEMBL)
HCRTR2 ProteinO43614 (Uniprot-TrEMBL)
HRASProteinP01112 (Uniprot-TrEMBL)
HRH1 ProteinP35367 (Uniprot-TrEMBL)
HTR2A ProteinP28223 (Uniprot-TrEMBL)
HTR2B ProteinP41595 (Uniprot-TrEMBL)
HTR2CProteinP28335 (Uniprot-TrEMBL)
HXA MetaboliteCHEBI:17120 (ChEBI)
Heterotrimeric G-protein Gq/11 ComplexREACT_5130 (Reactome)
Hist MetaboliteCHEBI:18295 (ChEBI)
IMetaboliteCHEBI:16595 (ChEBI)
KALRN ProteinO60229 (Uniprot-TrEMBL)
KISS1ProteinQ15726 (Uniprot-TrEMBL)
KISS1R ProteinQ969F8 (Uniprot-TrEMBL)
KRASProteinP01116 (Uniprot-TrEMBL)
L-Arg MetaboliteCHEBI:16467 (ChEBI)
L-Lys MetaboliteCHEBI:18019 (ChEBI)
L-Orn MetaboliteCHEBI:15729 (ChEBI)
LPA MetaboliteCHEBI:52288 (ChEBI)
LPAR1 ProteinQ92633 (Uniprot-TrEMBL)
LPAR2 ProteinQ9HBW0 (Uniprot-TrEMBL)
LPAR3 ProteinQ9UBY5 (Uniprot-TrEMBL)
LPAR4 ProteinQ99677 (Uniprot-TrEMBL)
LPAR5 ProteinQ9H1C0 (Uniprot-TrEMBL)
LPAR6 ProteinP43657 (Uniprot-TrEMBL)
LTB4 MetaboliteCHEBI:15647 (ChEBI)
LTB4R ProteinQ15722 (Uniprot-TrEMBL)
LTB4R2 ProteinQ9NPC1 (Uniprot-TrEMBL)
LTC4 MetaboliteCHEBI:16978 (ChEBI)
LTD4 MetaboliteCHEBI:28666 (ChEBI)
LTE4 MetaboliteCHEBI:15650 (ChEBI)
LXA4 MetaboliteCHEBI:6498 (ChEBI)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ComplexREACT_22589 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ComplexREACT_22865 (Reactome)
Ligand GPCR complexes that activate Gq/11ComplexREACT_18247 (Reactome)
Ligands of GPCRs that activate Gq/11MetaboliteREACT_23264 (Reactome)
MCHR1 ProteinQ99705 (Uniprot-TrEMBL)
MCHR2 ProteinQ969V1 (Uniprot-TrEMBL)
MLNProteinP12872 (Uniprot-TrEMBL)
MLNR ProteinO43193 (Uniprot-TrEMBL)
MMP3ProteinP08254 (Uniprot-TrEMBL)
MT-RNR2ProteinQ8IVG9 (Uniprot-TrEMBL)
NAd MetaboliteCHEBI:18357 (ChEBI)
NMBProteinP08949 (Uniprot-TrEMBL)
NMSProteinQ5H8A3 (Uniprot-TrEMBL)
NMUProteinP48645 (Uniprot-TrEMBL)
NMUR1 ProteinQ9HB89 (Uniprot-TrEMBL)
NMUR2 ProteinQ9GZQ4 (Uniprot-TrEMBL)
NPFFProteinO15130 (Uniprot-TrEMBL)
NPFFR1 ProteinQ9GZQ6 (Uniprot-TrEMBL)
NPFFR2 ProteinQ9Y5X5 (Uniprot-TrEMBL)
NPSProteinP0C0P6 (Uniprot-TrEMBL)
NPSR1 ProteinQ6W5P4 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
NTSProteinP30990 (Uniprot-TrEMBL)
NTSR1 ProteinP30989 (Uniprot-TrEMBL)
NTSR2 ProteinO95665 (Uniprot-TrEMBL)
Neurokinin A peptide ProteinP20366 (Uniprot-TrEMBL)
O-octanoyl-L-serine-GHRL-1ProteinQ9UBU3-1 (Uniprot-TrEMBL)
OLEA MetaboliteCHEBI:16196 (ChEBI)
OPN4 ProteinQ9UHM6 (Uniprot-TrEMBL)
OXTProteinP01178 (Uniprot-TrEMBL)
OXTR ProteinP30559 (Uniprot-TrEMBL)
P2RY1 ProteinP47900 (Uniprot-TrEMBL)
P2RY10 ProteinO00398 (Uniprot-TrEMBL)
P2RY11 ProteinQ96G91 (Uniprot-TrEMBL)
P2RY2 ProteinP41231 (Uniprot-TrEMBL)
P2RY6 ProteinQ15077 (Uniprot-TrEMBL)
PAF MetaboliteCHEBI:52450 (ChEBI)
PALM MetaboliteCHEBI:15756 (ChEBI)
PGE2 MetaboliteCHEBI:15551 (ChEBI)
PGF2a MetaboliteCHEBI:15553 (ChEBI)
PI3K alphaComplexREACT_12697 (Reactome)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PLC beta G alpha ComplexREACT_17363 (Reactome)
PLC-betaProteinREACT_15673 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 ProteinQ15147 (Uniprot-TrEMBL)
PMCHProteinP20382 (Uniprot-TrEMBL)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
PRKCAProteinP17252 (Uniprot-TrEMBL)
PROK1 ProteinP58294 (Uniprot-TrEMBL)
PROK2 ProteinQ9HC23 (Uniprot-TrEMBL)
PROKR1 ProteinQ8TCW9 (Uniprot-TrEMBL)
PROKR2 ProteinQ8NFJ6 (Uniprot-TrEMBL)
PTAFR ProteinP25105 (Uniprot-TrEMBL)
PTGER1 ProteinP34995 (Uniprot-TrEMBL)
PTGFR ProteinP43088 (Uniprot-TrEMBL)
Pentadecanoic acid MetaboliteCHEBI:42504 (ChEBI)
Phospho-Ribosomal protein S6 kinaseREACT_12696 (Reactome)
Protein Kinase C, alpha type DAGComplexREACT_18539 (Reactome)
QRFPProteinP83859 (Uniprot-TrEMBL)
QRFPR ProteinQ96P65 (Uniprot-TrEMBL)
RAF/MAP kinase cascadePathwayREACT_634 (Reactome) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
RGS proteins active for G alpha REACT_24580 (Reactome)
RGZ MetaboliteCHEBI:50122 (ChEBI)
Ribosomal protein S6 kinaseREACT_13229 (Reactome)
SAA1ProteinP0DJI8 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
Substance P peptide ProteinP20366 (Uniprot-TrEMBL)
TAC3ProteinQ9UHF0 (Uniprot-TrEMBL)
TACR1 ProteinP25103 (Uniprot-TrEMBL)
TACR2 ProteinP21452 (Uniprot-TrEMBL)
TACR3 ProteinP29371 (Uniprot-TrEMBL)
TBXA2RProteinP21731 (Uniprot-TrEMBL)
TRHProteinP20396 (Uniprot-TrEMBL)
TRHR ProteinP34981 (Uniprot-TrEMBL)
TRIO ProteinO75962 (Uniprot-TrEMBL)
TRIO family RhoGEFsProteinREACT_20038 (Reactome)
TXA2 MetaboliteCHEBI:15627 (ChEBI)
UDP MetaboliteCHEBI:17659 (ChEBI)
UTS2BProteinQ765I0 (Uniprot-TrEMBL)
UTS2ProteinO95399 (Uniprot-TrEMBL)
UTS2R ProteinQ9UKP6 (Uniprot-TrEMBL)
Valerate MetaboliteCHEBI:31011 (ChEBI)
XCL1 ProteinP47992 (Uniprot-TrEMBL)
XCL2 ProteinQ9UBD3 (Uniprot-TrEMBL)
XCR1 ProteinP46094 (Uniprot-TrEMBL)
p-6Y-EGFR ProteinP00533 (Uniprot-TrEMBL)
p-ERK1/2/5ProteinREACT_13301 (Reactome)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_12487 (Reactome)
ADPArrowREACT_12622 (Reactome)
ADRBK1REACT_19213 (Reactome)
ATPREACT_12487 (Reactome)
ATPREACT_12622 (Reactome)
CCKBRREACT_121113 (Reactome)
CREB1REACT_12622 (Reactome)
DAGArrowREACT_960 (Reactome)
DAGREACT_18303 (Reactome)
EGFRREACT_121381 (Reactome)
G-protein alpha ArrowREACT_22263 (Reactome)
G-protein alpha REACT_19172 (Reactome)
G-protein alpha REACT_19213 (Reactome)
G-protein alpha REACT_19270 (Reactome)
G-protein alpha REACT_19301 (Reactome)
G-protein alpha REACT_19325 (Reactome)
G-protein alpha REACT_22425 (Reactome)
G-protein alpha mim-catalysisREACT_19186 (Reactome)
G-protein beta-gamma complexArrowREACT_22263 (Reactome)
G-protein beta-gamma complexREACT_22425 (Reactome)
GASTREACT_121113 (Reactome)
GDPArrowREACT_121377 (Reactome)
GDPArrowREACT_15291 (Reactome)
GPCRs that activate Gq/11ArrowREACT_22263 (Reactome)
GRB2

SOS1 HB-EGF

p-6Y-EGFR		mim-catalysisREACT_121377 (Reactome)
GRB2 SOS1REACT_121250 (Reactome)
GRK5REACT_19325 (Reactome)
GTPREACT_121377 (Reactome)
GTPREACT_15291 (Reactome)
HB-EGF p-6Y-EGFR dimerREACT_121250 (Reactome)
HBEGFArrowREACT_121027 (Reactome)
HBEGFREACT_121381 (Reactome)
Heterotrimeric G-protein Gq/11 REACT_22436 (Reactome)
IArrowREACT_960 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ArrowREACT_15291 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		REACT_15291 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		mim-catalysisREACT_15291 (Reactome)
Ligand GPCR complexes that activate Gq/11REACT_22436 (Reactome)
Ligands of GPCRs that activate Gq/11ArrowREACT_22263 (Reactome)
MMP3mim-catalysisREACT_121027 (Reactome)
PI3K alphaREACT_19172 (Reactome)
PLC beta G alpha mim-catalysisREACT_960 (Reactome)
PLC-betaREACT_19270 (Reactome)
PRKCAREACT_18303 (Reactome)
Phospho-Ribosomal protein S6 kinaseArrowREACT_12487 (Reactome)
Phospho-Ribosomal protein S6 kinasemim-catalysisREACT_12622 (Reactome)
Protein Kinase C, alpha type DAGmim-catalysisREACT_120731 (Reactome)
REACT_120731 (Reactome) Gastrin activated PKC pathway leads to the induction of matrix metalloproteinase 3 (MMP3) synthesis (Reuben et al. 2002). The cleavage and autocatalysis steps to obtain the fully activated form of MMP3 have been omitted here.
REACT_121027 (Reactome) Gastrin can induce cleavage of pro-HBEGF via MMP3, releasing mature HBEGF. This event is based on evidence from mouse experiments (Suzuki et al. 1997).
REACT_121113 (Reactome) Gastrin receptors (gastric cholecystokinin B receptor, CCK-BR) mediate acid secretion from parietal cells, release of histamine from enterochromaffin-like (ECL) cells and contraction of smooth muscle (Ito et al. 1993).The hormone gastrin is the central regulator of gastric acid secretion and in addition, plays a prominent role in regulation of growth and differentiation of gastric and colonic mucosa.
REACT_121250 (Reactome) Cytoplasmic target proteins containing the SH2 domain can bind to activated EGFR. One such protein, growth factor receptor-bound protein 2 (GRB2), can bind activated EGFR with its SH2 domain whilst in complex with SOS through its SH3 domain. GRB2 can bind at either Y1068 and/or Y1086 autophosphorylation sites on the receptor (Batzer et al. 1994, Okutani et al. 1994).
REACT_121377 (Reactome) SOS1 is the guanine nucleotide exchange factor (GEF) for RAS. SOS1 activates RAS nucleotide exchange from the inactive form (bound to GDP) to an active form (bound to GTP) (Chardin et al. 1993).
REACT_121381 (Reactome) The heparin-binding EGF growth factor (HBEGF) is a member of the EGF family of growth factors that binds to and activates the EGF receptor EGFR/ErbB1 and ErbB4 (not shown here) (Higashiyama et al. 1991, Elenius et al. 1997). The details which describe receptor dimerisation on ligand binding and autophosphorylation from experiments in mice have been omitted here.
REACT_12487 (Reactome) The p90 ribosomal S6 kinases (RSK1-4) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. RSK family members are unusual among serine/threonine kinases in that they contain two distinct kinase domains, both of which are catalytically functional . The C-terminal kinase domain is believed to be involved in autophosphorylation, a critical step in RSK activation, whereas the N-terminal kinase domain, which is homologous to members of the AGC superfamily of kinases, is responsible for the phosphorylation of all known exogenous substrates of RSK.
RSKs can be activated by the ERKs (ERK1, 2, 5) in the cytoplasm as well as in the nucleus, they both have cytoplasmic and nuclear substrates, and they are able to move from nucleus to cytoplasm. Efficient RSK activation by ERKs requires its interaction through a docking site located near the RSK C terminus. The mechanism of RSK activation has been studied mainly with regard to ERK1 and ERK2. RSK activation leads to the phosphorylation of four essential residues Ser239, Ser381, Ser398, and Thr590, and two additional sites, Thr377 and Ser749 (the amino acid numbering refers to RSK1). ERK is thought to play at least two roles in RSK1 activation. First, activated ERK phosphorylates RSK1 on Thr590, and possibly on Thr377 and Ser381, and second, ERK brings RSK1 into close proximity to membrane-associated kinases that may phosphorylate RSK1 on Ser381 and Ser398.
Moreover, RSKs and ERK1/2 form a complex that transiently dissociates upon growth factor signalling. Complex dissociation requires phosphorylation of RSK1 serine 749, a growth factor regulated phosphorylation site located near the ERK docking site. Serine 749 is phosphorylated by the N-terminal kinase domain of RSK1 itself. ERK1/2 docking to RSK2 and RSK3 is also regulated in a similar way. The length of RSK activation following growth factor stimulation depends on the duration of the RSK/ERK complex, which, in turn, differs among the different RSK isoforms. RSK1 and RSK2 readily dissociate from ERK1/2 following growth factor stimulation stimulation, but RSK3 remains associated with active ERK1/2 longer, and also remains active longer than RSK1 and RSK2.

REACT_12622 (Reactome) CREB is phosphorylated at Serine 133 by RSK1/2/3.
REACT_15291 (Reactome) G alpha q protein (or Gq/11) consists of four family members (G-alpha 11, -alpha 14, -alpha 15 and -alpha q). It activates phospholipase C (PLC) (Dowal L et al, 2006). PLC hydrolyzes phosphatidylinositol (PIP2) to diacyl glycerol (DAG) and inositol triphosphate (IP3). DAG acts as a second messenger that activates protein kinase C (PKC) and IP3 can bind to IP3 receptors, particular calcium channels in the endoplasmic reticulum (ER). Calcium flow causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity.
REACT_18303 (Reactome) Diacylglycerol, produced by PLC beta-mediated PIP2 hydrolysis in G alpha (q) signalling, remains in the plasma membrane and binds Protein Kinase C alpha (PKC-alpha), causing PKC-alpha to translocate from the cytosol to the plasma membrane. PKC-alpha is thereby activated and phosphorylates target proteins.
REACT_19172 (Reactome) Phospholipase C activation is the classical signalling route for G alpha (q) but an additional mechanism is an inhibitory interaction between G alpha (q) and phosphatidylinositol 3-kinase alpha (PI3K alpha). There are several PI3K subtypes but only the p85 alpha/p110 alpha subtype (PI3K alpha) is a G alpha (q) effector (PMID: 18515384). Activated G alpha (q) inhibits PI3K alpha directly, in a GTP-dependent manner. G alpha(q) binding of PI3K competes with Ras, a PI3K activator (PMID: 16268778).
REACT_19186 (Reactome) When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region.
REACT_19213 (Reactome) GRK2 can inhibit GPCR signaling via phosphorylation-independent sequestration of Gq/11/14 subunits utilising its RGS homology (RH) domain. GRK2 may be an effector of activated Gq, initiating signalling cascades other than the classical PLC beta signalling associated with Gq.
REACT_19270 (Reactome) The active form of G protein alpha subunit q (Gq-alpha) was found to activate phospholipase C beta-1 (PLC-beta1), in investigations using bovine membranes. Subsequently, all 4 human isoforms have been shown to be activated by Gq, though activation of PLCbeta-4 is limited. In recombinant assays, several activated rat G alpha q family members were found to stimulate human PLC-beta isoforms with the same rank order of decreasing potency. PLC-beta1 stimulation was slightly more than for PLC-beta3; PLC-beta3 stimulation was 10-fold greater than for beta-2. PLC-beta2 is expressed specifically in hematopoietic cells. PLC-beta acts directly on Gq to accelerate hydrolysis of bound GTP, thus PLC-betas are GTPase activating proteins (GAPs). The crystal structure of the C-terminal region from Turkey PLC-beta, revealed a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The extent of the dimer interface and gel exclusion chromatography data suggest that PLC-betas are functionally dimeric.
REACT_19301 (Reactome) The Trio family of RhoA guanine nucleotide exchange factors (RhoGEFs) are directly activated by G alpha (q), possibly within a Gq:Trio:RhoA signalling complex, thereby linking Gq to RhoA-mediated processes such as cell migration, proliferation, and contraction. Like most other RhoGEFs, they have a tandem motif consisting of a Dbl homology (DH) and a pleckstrin homology (PH) domain. Trio and Duet have a number of other domains including an immunoglobin domains that may be involved in interacting with Rho, but the considerably smaller GEFT (p63RhoGEF) does not have any identifiable additional domains yet appears to be sufficient to mediate the activation of RhoA by G alpha (q). The structure represented by GEFT is proposed to represent the core of an ancient signal transduction pathway.
REACT_19325 (Reactome) GRKs are serine/threonine kinases that phosphorylate GPCRs leading to receptor desensitization. GRK5 appears to be the predominant regulator of PAR1 desensitization in endothelial cells.
REACT_22263 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (q) and the beta:gamma dimer then participate in separate signaling cascades. Although G protein dissociation has been contested (e.g. Bassi et al. 1996), recent in vivo experiments have demonstrated that dissociation does occur, though possibly not to completion (Lambert 2008).
REACT_22425 (Reactome) The classical model of G-protein signaling suggests that the G-protein dissociates upon GPCR activation. The active G alpha (q) subunit then participates in signaling, until its intrinsic GTPase activity degrades the bound GTP to GDP. The inactive G alpha (q):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates.
REACT_22436 (Reactome) Numerous functionally unrelated GPCRs couple with the Gq G-protein subtype.
REACT_960 (Reactome) Phospholipase C (PLC) isozymes are a group of related proteins that cleave the polar head group from inositol phospholipids, typically in response to signals from cell surface receptors. They hydrolyze the highly phosphorylated lipid phosphatidylinositol 4,5-bisphosphate (PIP2) generating two products: inositol 1,4,5-trisphosphate (IP3), a universal calcium-mobilizing second messenger, and diacylglycerol (DAG), an activator of protein kinase C. PLC-beta isoforms are regulated by heterotrimeric GTP-binding proteins. PLC-beta 1 and 3 are widely expressed, with the highest concentrations found in (differing) specific regions of the brain. PLC-beta 2 is expressed at highest levels in cells of hematopoeitic origin; it is involved in leukocyte signaling and host defense. PLC-beta 4 is highly concentrated in cerebellar Purkinje and granule cells, the median geniculate body, whose axons terminate in the auditory cortex, and the lateral geniculate nucleus, where most retinal axons terminate in a visuotopic representation of each half of the visual field.
RGS proteins active for G alpha ArrowREACT_19186 (Reactome)
Ribosomal protein S6 kinaseREACT_12487 (Reactome)
TRIO family RhoGEFsREACT_19301 (Reactome)
p-ERK1/2/5mim-catalysisREACT_12487 (Reactome)
p-S133-CREB1ArrowREACT_12622 (Reactome)
p21 RAS GDPREACT_121377 (Reactome)
p21 RAS GTPArrowREACT_121377 (Reactome)
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