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

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11, 30, 585468, 5925, 4029, 4519272, 34441336573, 18, 236, 7, 42, 43, 5150334, 355638, 3924cytosolnucleoplasmAVPR1B HB-EGF:p-6Y-EGFRdimerG-protein beta-gammacomplexGNB2 LPAR5 Ligand:GPCRcomplexes thatactivate Gq/11HXA LTD4 KISS1(68-121) GNB5 PIK3R3 GTP GNG7 LTB4 ADRA1B GCGR CHRM3 5HT TRH(84-86) EDN2 AGTR1 KISS1R p-4S,T231,T365-RPS6KA3 ANXA1 LPAR1 PMCH(147-165) P2RY10 PIK3R1 TRIO ADRA1D OXTR XCR1 NMUR2 SAA1(19-122) P2RY2 GDP P2RY6 MCHR2 P2RY11 CHRM1 Bradykinin HBEGF(63-148) CCKAR HBEGF(63-148) GTP CH3COO- GNA14 ADP GNG3 LPA OXTR UDP TRH(227-229) PTGFR RGS proteins activefor G alpha (q)GNRHR2 GNG4 GTP TRHR GPRC6A ADPPTGER1 CREB1Photon XCL2 GNG3 F2R(27-425) P2RY6 AcCho Acyl Ghrelin LTB4R2 EDN2 I(1,4,5)P3 HCRTR1 P2RY11 DecS-GHRL-1(24-50) OXT(20-28) NMS F2RL3(18-385) EDN1 EDN3(97-117) TRH(186-188) PROKR1 TAC3 ADRBK1 ADRA1A TAC1(58-68) Basic L-amino acids GNB5 LTE4 LXA4 LPAR3 GRM5 5HT GNGT2 GNAQ GNAQ GNG10 GPRC6A GRK5CYSLTR2 GNG3 ATP GNA15 F2RL1(37-397) GNA14 P2RY1 GNA14 XCL1,XCL2 GNA11 GRP(24-50) FFAR2 GPRC6A KISS1(68-121) UTS2 KISS1R PROKR2 TACR2 NMB(47-56) PLC beta:G alpha(q/11)MCHR1 CCKAR ARHGEF25 AGT(34-41) FFAR1 ligands GTP Basic L-amino acids GNB2 TRHR PGE2 GCG(53-81) LTB4R2 UTS2 GNB3 CCKAR HTR2A GCG(53-81) PLCB3 TRH(114-116) ADRA1A PROK2 P2RY6 GDPADR GNA11 P2RY1 GPR17 MLNR GNA15 PGE2 AVP(20-28) p-T202,Y204-MAPK3 GNAQ LPAR2 PIK3CA GNAQ GNAQ NPS NPFF(69-76) Ca2+ TRH(114-116) GTP HCRT(34-66) P2RY2 GNA14 GTP GNB1 P2RY2 I(1,4,5)P3LPAR6 Protein Kinase C,alpha type: DAGEDNRB QRFP HRH1 OXT(20-28) ADP QRFPR NTSR1 RAF/MAP kinasecascadeCCK PAF LPAR4 GNG3 TAC1(98-107) NPS TACR3 NPFFR1 PI(4,5)P2 Pentadecanoic acid GNAQ NPSR1 UTS2 HCRTR2 TAC1(58-68) TRIO GPR4 BRS3 O-octanoyl-L-serine-GHRL-1(24-51) P2RY10 GAST(76-92) CYSLTR1,CYSLTR2 CHRM3 G-protein alpha(q/11): GTPRGZ P2RY10 NPFFR2 PGF2a XCL1 Ligand:GPCRcomplexesthatactivateGq/11:Heterotrimeric G-protein Gq (inactive)LPAR5 GCGR thrombin heavy chain AVP(20-28) EDNRA PTGFR GNA11 CHRM1 HBEGF(20-62)PIK3R2 RGS18 LPAR2 FFAR2 PGE2 GNG13 GHSR DecS-GHRL-1(24-51) GPR4 CCKBR UTS2B FFAR1 p-S133-CREB1TRH(135-137) GNG7 GRM1 MLNR TACR2 APP(672-713) GHSR GNG5 Bradykinin TACR2 L-Glu GTPMLN(26-47) UTS2B HCRT(34-66) pH sensing receptors TRH(152-154) LTB4R EGFRG-protein alpha(q/11):Trio familyRhoGEFsCCK ATPTACR1 TRH(152-154) RPS6KA2 CHRM5 F2RL3(18-385) G-protein alpha(q):GRK2PMCH(147-165) p21 RAS:GTPHCOOH GNA15 MT-RNR2 PIK3R2 NPFFR1 G-protein alpha(q/11)LTB4 GNRH2(24-33) NTS(151-163) QRFPR O-octanoyl-L-serine-GHRL-1(24-51) GNG2 LPAR3 XCL2 PROKR2 CCK OPN4 GNRH1(24-33) QRFP PLCB4 NPFF(69-76) RGS2 GPR132 AcCho AVPR1A,B O-octanoyl-L-serine-GHRL-1(24-50) GRM5 KISS1(68-121) GNAQ Bombesin-like receptor ADR HCRT(34-66) GNA15 GDP RGZ ADRBK1GNG7 SAA1(19-122) FPR2 Hist thrombin heavy chain Bradykinin GRB2-1:SOS1XCL2 EtCOO- or C2H5COO- UTS2R PROK2 GRP(24-50) NMUR2 LTB4 MMP3UTS2R OLEA Ligands of GPCRsthat activate Gq/11MCHR2 NTSR2 GNB2 ATP Valerate G-protein alpha(q/11):PI3K alphaNMU Pentadecanoic acid TBXA2R GNGT2 AVP(20-28) HTR2C Ribosomal protein S6kinaseCYSLTR2 CHRM5 FFAR3 NPS TRH(84-86) TACR1 GRP(24-50) LXA4 TXA2 GNG2 NMB(47-56) QRFP GNG4 XCR1 DAG GAST(76-92) GHSR GNG13 NPFF(69-76) GNG8 AcCho NPS GNGT1 PLCB3 GNB4 PLCB2 ATP GNA15 ADRA1B ATPMMP3(100-477)HRH1 TACR2 p-6Y-EGFR TAC1(98-107) GNRH2(24-33) LTB4R H+ TBXA2R PLCB1 GNAQ GNG12 QRFPR NPFFR2 UTS2R HCRTR1 p21 RAS:GDPLPAR4 GNRHR2 TRHR PAF LPAR2 GNA11 HCRT(34-66) LTB4R DecS-GHRL-1(24-50) GNRH1(24-33) CCKBR FFAR2 PALM LTB4 NMBR CHRM1, 3, 5 BRS3 TAC3 EDNRB Hist EDN3(97-117) GNG4 NTSR1 FPR2 ligands TACR3 GNAQ CHRM1 KISS1R GNA11 CCL23-2 AGTR1 NPSR1 PTGER1 OXTR F2R(27-425) SOS1 GNRH2(24-33) FPR2 PTGFR NPFF(69-76) MT-RNR2 thrombin heavy chain GNA15 Valerate EDN1 RPS6KA3 GNG2 GNB5 HRAS GRB2-1 LPAR5 OXT(20-28) NMS GNA14 GNG13 MCHR1 NMBR AGT(34-41) NMB(47-56) ADRA1D GPR17 NMUR2 GNG4 CCKBR GNA14 GPR65 CYSLTR1 UDP BDKRB1 TRH(152-154) Photon PIK3CA GNG8 PMCH(147-165) UTS2R FPR2 EDNRB CHRM5 GNA11 KRAS TACR1 TAC1(98-107) DDCX PAF L-Glu GRM1 EtCOO- or C2H5COO- GNB4 NMS NTS(151-163) 5HT HTR2C AVPR1A GNB1 GNA11 CASR Bradykinin receptor TAC1(98-107) F2RL1(37-397) CYSLTR1 LPAR6 p-T185,Y187-MAPK1 NMUR1 GPR132 BUT PTGER1 thrombin light chain O-octanoyl-L-serine-GHRL-1(24-51) APP(672-713) PROK2 GNA14 P2RY10 RGS3 Ca2+ GNA11 GAST(76-92) GNGT2 LTE4 HXA OLEA ADP NTS(151-163) Photon GPR68 FFAR2 ligands thrombin light chain thrombin light chain PROKR1,PROKR2 P2RY1 PROK1,PROK2 MT-RNR2 GNA11 CASR FFAR3 GNA14 ARHGEF25 PMCH(147-165) CASR XCR1 EDN2 QRFP GNG8 DAG 5HT P2RY6 AVP(20-28) TRH(227-229) GTP HCOOH NPFFR1,NPFFR2 HCRTR1 DecS-GHRL-1(24-51) GPR68 H+ TAC3 HBEGF(20-208)LPA GNA15 GNRH ligands HBEGF(63-148)CASR KISS1R HCRTR2 NTS(151-163) HCRTR2 GNGT1 BDKRB2 TXA2 GNAQ LTB4R2 PROKR1 BUT GRPR PGF2a NTSR2 LPAR6 Hist GNB4 OXTR GNG5 CCL23-2 RGSL1 TBXA2R TRH GNB5 P2RY1 FPR2 GNG5 LPAR4 GRK5 PALM Photon MLN(26-47) LPAR1,2,3,5 p-6Y-EGFR AGT(34-41) GAST(76-92) PLCB1 ADPL-Glu thrombin heavy chain GPR4 GHSR ADR, NAd GNG7 HCRT(70-97) PLCB3 EDNRA GDP Gastrin:CCKBRGNRHR CCKBR GCGR TXA2 RGZ AVPR1B PAF FFAR3 PTAFR HTR2B TRH(227-229) CCKBR G-protein alpha(q/11):GDPPROKR1 GRPR PLCB2 GDPGNG11 PROK1 NAd AVPR1A GPR17 NMUR1 NPFFR1 GCG(53-81) NTSR1,NTSR2 PLCB4 BDKRB1 GnRH receptor GNA15 LPAR6 GPCRs that activateGq/11TRHR EDN3(97-117) DecS-GHRL-1(24-51) GNA15 HTR2A-C P2RY11 XCL1 G-protein alpha(q):GRK5ADP TACR3 NMU NPSR1 GNGT1 PLCB2 Basic L-amino acids GNG12 H+ DecS-GHRL-1(24-50) TACR1 NMUR1,NMUR2 FFAR1 PGF2a GNB4 FFAR3 ligands LPAR1 GNRHR2 GNA14 GNA14 PROK1 GRB2-1 NAd BRS3 TRIO family RhoGEFsGNG10 GPR65 EDN1 KALRN PLCB4 GNA15 thrombin light chain GNRH1(24-33) UDP GNG11 HTR2A OLEA TACR3 PLCB1 PGF2a MCHR1,MCHR2 HBEGF(149-208)p-ERK1/2/5OPN4 APP(672-713) NMBR TRH(114-116) GNG5 HRAS FFAR2 KALRN PLC-betaAGTR1 PLCB3 AVPR1A FFAR1 TBXA2R HTR2C CCL23-2 MCHR2 GNA15 MLNR ANXA1 ADRA1A p-4S,T359,T573-RPS6KA1 GRB2:SOS1:HB-EGF:p-6Y-EGFRHCRT(70-97) F2RL3(18-385) HCRT(70-97) RGS21 TRH(135-137) DAGGNG13 ANXA1 Proteinase-activated receptors BUT GTP TRH(186-188) GTP NPSR1 LTB4R,LTB4R2 GNA11 LXA4 TRH(84-86) GNB2 SAA1(19-122) GRPR LPA RGS19 PLCB1 GNG10 EDNRA GNB3 NRAS GRM1 TRH(186-188) p-T218,Y220-MAPK7 GNG10 FFAR1 PGE2 PLCB2 TAC3 Hist TAC1(58-68) NMU MLN(26-47) GNG2 GNAQ P2RY2 Pentadecanoic acid ADRA1B MLN(26-47) GNB1 MCHR1 LPAR4 BDKRB1 PROK1 CHRM3 LTC4 GDP CYSLTR1 GNRHR KRAS GPRC6A NMUR1 GNA14 GNA15 PTGFR LTD4 HTR2B GPR132 NTSR1 PLC-beta:G-alpha(q/11):PIP2EDNRA,EDNRB HRH1 H+ GPR17 GNG11 DDCX GCG(53-81) ATP GNG12 AVPR1B PIK3R3 GPR68 OPN4 DDCX CH3COO- F2RL1(37-397) HCRT(70-97) GTP FFAR3 PTAFR GNAQ PROKR2 GNB3 GNA11 Ca2+ NRAS Ca2+ ADR UDP p-4S,T356,T570-RPS6KA2 UTS2,UTS2B GNGT1 ADRA1D GNAQ QRFPR PLC-beta:G-alpha(q/11):DAG:IP3LPAR1 LTC4 HTR2A GNB1 OXT(20-28) GTPPTAFR ADRA1A,B,D TAC1(58-68) NMUR2 Bradykinin PRKCA HXA UTS2B CCK CH3COO- NMU GNG8 Phospho-Ribosomalprotein S6 kinaseGNA15 GAST(76-92)GNRHR Endothelin NAd NPFFR2 HCRTR1 GAST(76-92) KISS1(68-121) OPN4 BDKRB2 LTC4 RPS6KA1 TXA2 HRH1 GPR65 HTR2B GNA11 O-octanoyl-L-serine-GHRL-1(24-50) TRH(135-137) GRM1,GRM5 PIK3R1 Ligand:GPCRcomplexesthatactivateGq/11:Heterotrimeric G-protein Gq (active)F2R(27-425) CYSLTR2 LTD4 PTAFR GNA14 GCGR PI3K alphaNTSR2 LTE4 F2RL2(22-374) CCKAR,CCKBR HCRTR2 PLCB4 AcCho NMS AGT(34-41) P2RY11 Bombesin-like peptide BDKRB2 LPAR3 GNA11 PTGER1 SOS1 EtCOO- or C2H5COO- Valerate GNG12 PALM PRKCAAGTR1 MLNR F2RL2(22-374) GNG11 O-octanoyl-L-serine-GHRL-1(24-50) XCL1 HeterotrimericG-protein Gq/11(inactive)HCOOH GRM5 CCKBRXCR1 LPA Cysteinyl leukotrienes GPRC6A ligands F2RL2(22-374) GNA14 Effects of PIP2hydrolysisGNGT2 L-Glu GNB3 321, 173241, 471, 171, 171, 171, 1710, 15, 48, 531, 175, 9, 12, 14, 16...1, 1731, 461, 17


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) View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 881907
Reactome-version 
Reactome version: 62
Reactome Author 
Reactome Author: Jassal, Bijay, Tripathi, S

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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

View all...
NameTypeDatabase referenceComment
5HT MetaboliteCHEBI:28790 (ChEBI)
ADP MetaboliteCHEBI:16761 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ADR MetaboliteCHEBI:28918 (ChEBI)
ADR, NAd R-ALL-390627 (Reactome)
ADRA1A ProteinP35348 (Uniprot-TrEMBL)
ADRA1A,B,D R-HSA-390684 (Reactome)
ADRA1B ProteinP35368 (Uniprot-TrEMBL)
ADRA1D ProteinP25100 (Uniprot-TrEMBL)
ADRBK1 ProteinP25098 (Uniprot-TrEMBL)
ADRBK1ProteinP25098 (Uniprot-TrEMBL)
AGT(34-41) ProteinP01019 (Uniprot-TrEMBL)
AGTR1 ProteinP30556 (Uniprot-TrEMBL)
ANXA1 ProteinP04083 (Uniprot-TrEMBL)
APP(672-713) ProteinP05067 (Uniprot-TrEMBL)
ARHGEF25 ProteinQ86VW2 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
AVP(20-28) ProteinP01185 (Uniprot-TrEMBL)
AVPR1A ProteinP37288 (Uniprot-TrEMBL)
AVPR1A,B R-HSA-388458 (Reactome)
AVPR1B ProteinP47901 (Uniprot-TrEMBL)
AcCho MetaboliteCHEBI:15355 (ChEBI)
Acyl Ghrelin R-HSA-422096 (Reactome)
BDKRB1 ProteinP46663 (Uniprot-TrEMBL)
BDKRB2 ProteinP30411 (Uniprot-TrEMBL)
BRS3 ProteinP32247 (Uniprot-TrEMBL)
BUT MetaboliteCHEBI:30772 (ChEBI)
Basic L-amino acids R-ALL-420746 (Reactome)
Bombesin-like peptide R-HSA-375360 (Reactome)
Bombesin-like receptor R-HSA-375362 (Reactome)
Bradykinin ProteinP01042 (Uniprot-TrEMBL)
Bradykinin receptor R-HSA-374323 (Reactome)
CASR ProteinP41180 (Uniprot-TrEMBL)
CCK ProteinP06307 (Uniprot-TrEMBL)
CCKAR ProteinP32238 (Uniprot-TrEMBL)
CCKAR,CCKBR R-HSA-388518 (Reactome)
CCKBR ProteinP32239 (Uniprot-TrEMBL)
CCKBRProteinP32239 (Uniprot-TrEMBL)
CCL23-2 ProteinP55773-2 (Uniprot-TrEMBL)
CH3COO- MetaboliteCHEBI:15366 (ChEBI)
CHRM1 ProteinP11229 (Uniprot-TrEMBL)
CHRM1, 3, 5 R-HSA-390660 (Reactome)
CHRM3 ProteinP20309 (Uniprot-TrEMBL)
CHRM5 ProteinP08912 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
CYSLTR1 ProteinQ9Y271 (Uniprot-TrEMBL)
CYSLTR1,CYSLTR2 R-HSA-416385 (Reactome)
CYSLTR2 ProteinQ9NS75 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Cysteinyl leukotrienes R-ALL-416372 (Reactome)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
DDCX MetaboliteCHEBI:30805 (ChEBI)
DecS-GHRL-1(24-50) ProteinQ9UBU3-1 (Uniprot-TrEMBL)
DecS-GHRL-1(24-51) ProteinQ9UBU3-1 (Uniprot-TrEMBL)
EDN1 ProteinP05305 (Uniprot-TrEMBL)
EDN2 ProteinP20800 (Uniprot-TrEMBL)
EDN3(97-117) ProteinP14138 (Uniprot-TrEMBL)
EDNRA ProteinP25101 (Uniprot-TrEMBL)
EDNRA,EDNRB R-HSA-388547 (Reactome)
EDNRB ProteinP24530 (Uniprot-TrEMBL)
EGFRProteinP00533 (Uniprot-TrEMBL)
Effects of PIP2 hydrolysisPathwayR-HSA-114508 (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.
Endothelin R-HSA-388544 (Reactome)
EtCOO- or C2H5COO- MetaboliteCHEBI:30768 (ChEBI)
F2R(27-425) ProteinP25116 (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.
F2RL1(37-397) ProteinP55085 (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.
F2RL2(22-374) ProteinO00254 (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.
F2RL3(18-385) ProteinQ96RI0 (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)
FFAR1 ligands R-ALL-400427 (Reactome)
FFAR2 ProteinO15552 (Uniprot-TrEMBL)
FFAR2 ligands R-ALL-444210 (Reactome)
FFAR3 ProteinO14843 (Uniprot-TrEMBL)
FFAR3 ligands R-ALL-444074 (Reactome)
FPR2 ProteinP25090 (Uniprot-TrEMBL)
FPR2 ligands R-HSA-444472 (Reactome)
G-protein alpha (q):GRK2ComplexR-HSA-416515 (Reactome)
G-protein alpha (q):GRK5ComplexR-HSA-416517 (Reactome)
G-protein alpha (q/11): GTPComplexR-HSA-114534 (Reactome)
G-protein alpha (q/11):GDPComplexR-HSA-114556 (Reactome)
G-protein alpha (q/11):PI3K alphaComplexR-HSA-416356 (Reactome)
G-protein alpha

(q/11):Trio family

RhoGEFs
ComplexR-HSA-400608 (Reactome)
G-protein alpha (q/11)ComplexR-HSA-374848 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
GAST(76-92) ProteinP01350 (Uniprot-TrEMBL)
GAST(76-92)ProteinP01350 (Uniprot-TrEMBL)
GCG(53-81) ProteinP01275 (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)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GNRH ligands R-HSA-873938 (Reactome)
GNRH1(24-33) ProteinP01148 (Uniprot-TrEMBL)
GNRH2(24-33) ProteinO43555 (Uniprot-TrEMBL)
GNRHR ProteinP30968 (Uniprot-TrEMBL)
GNRHR2 ProteinQ96P88 (Uniprot-TrEMBL)
GPCRs that activate Gq/11ComplexR-HSA-791493 (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)
GPRC6A ligands R-ALL-420706 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1:SOS1ComplexR-HSA-109797 (Reactome)
GRB2:SOS1:HB-EGF:p-6Y-EGFRComplexR-HSA-2179409 (Reactome)
GRK5 ProteinP34947 (Uniprot-TrEMBL)
GRK5ProteinP34947 (Uniprot-TrEMBL)
GRM1 ProteinQ13255 (Uniprot-TrEMBL)
GRM1,GRM5 R-HSA-420566 (Reactome)
GRM5 ProteinP41594 (Uniprot-TrEMBL)
GRP(24-50) ProteinP07492 (Uniprot-TrEMBL)
GRPR ProteinP30550 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Gastrin:CCKBRComplexR-HSA-870262 (Reactome)
GnRH receptor R-HSA-391368 (Reactome)
H+ MetaboliteCHEBI:15378 (ChEBI)
HB-EGF:p-6Y-EGFR dimerComplexR-HSA-2179410 (Reactome)
HBEGF(149-208)ProteinQ99075 (Uniprot-TrEMBL)
HBEGF(20-208)ProteinQ99075 (Uniprot-TrEMBL)
HBEGF(20-62)ProteinQ99075 (Uniprot-TrEMBL)
HBEGF(63-148) ProteinQ99075 (Uniprot-TrEMBL)
HBEGF(63-148)ProteinQ99075 (Uniprot-TrEMBL)
HCOOH MetaboliteCHEBI:30751 (ChEBI)
HCRT(34-66) ProteinO43612 (Uniprot-TrEMBL)
HCRT(70-97) ProteinO43612 (Uniprot-TrEMBL)
HCRTR1 ProteinO43613 (Uniprot-TrEMBL)
HCRTR2 ProteinO43614 (Uniprot-TrEMBL)
HRAS ProteinP01112 (Uniprot-TrEMBL)
HRH1 ProteinP35367 (Uniprot-TrEMBL)
HTR2A ProteinP28223 (Uniprot-TrEMBL)
HTR2A-C R-HSA-391030 (Reactome)
HTR2B ProteinP41595 (Uniprot-TrEMBL)
HTR2C ProteinP28335 (Uniprot-TrEMBL)
HXA MetaboliteCHEBI:17120 (ChEBI)
Heterotrimeric

G-protein Gq/11

(inactive)
ComplexR-HSA-114557 (Reactome)
Hist MetaboliteCHEBI:18295 (ChEBI)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
KALRN ProteinO60229 (Uniprot-TrEMBL)
KISS1(68-121) ProteinQ15726 (Uniprot-TrEMBL)
KISS1R ProteinQ969F8 (Uniprot-TrEMBL)
KRAS ProteinP01116 (Uniprot-TrEMBL)
L-Glu MetaboliteCHEBI:29985 (ChEBI)
LPA MetaboliteCHEBI:52288 (ChEBI)
LPAR1 ProteinQ92633 (Uniprot-TrEMBL)
LPAR1,2,3,5 R-HSA-419369 (Reactome)
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)
LTB4R,LTB4R2 R-HSA-416401 (Reactome)
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 (active)
ComplexR-HSA-749447 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (inactive)
ComplexR-HSA-749451 (Reactome)
Ligand:GPCR

complexes that

activate Gq/11
ComplexR-HSA-380110 (Reactome)
Ligands of GPCRs that activate Gq/11ComplexR-HSA-791492 (Reactome)
MCHR1 ProteinQ99705 (Uniprot-TrEMBL)
MCHR1,MCHR2 R-HSA-947667 (Reactome)
MCHR2 ProteinQ969V1 (Uniprot-TrEMBL)
MLN(26-47) ProteinP12872 (Uniprot-TrEMBL)
MLNR ProteinO43193 (Uniprot-TrEMBL)
MMP3(100-477)ProteinP08254 (Uniprot-TrEMBL)
MMP3ProteinP08254 (Uniprot-TrEMBL)
MT-RNR2 ProteinQ8IVG9 (Uniprot-TrEMBL)
NAd MetaboliteCHEBI:18357 (ChEBI)
NMB(47-56) ProteinP08949 (Uniprot-TrEMBL)
NMBR ProteinP28336 (Uniprot-TrEMBL)
NMS ProteinQ5H8A3 (Uniprot-TrEMBL)
NMU ProteinP48645 (Uniprot-TrEMBL)
NMUR1 ProteinQ9HB89 (Uniprot-TrEMBL)
NMUR1,NMUR2 R-HSA-964805 (Reactome)
NMUR2 ProteinQ9GZQ4 (Uniprot-TrEMBL)
NPFF(69-76) ProteinO15130 (Uniprot-TrEMBL)
NPFFR1 ProteinQ9GZQ6 (Uniprot-TrEMBL)
NPFFR1,NPFFR2 R-HSA-389406 (Reactome)
NPFFR2 ProteinQ9Y5X5 (Uniprot-TrEMBL)
NPS ProteinP0C0P6 (Uniprot-TrEMBL)
NPSR1 ProteinQ6W5P4 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
NTS(151-163) ProteinP30990 (Uniprot-TrEMBL)
NTSR1 ProteinP30989 (Uniprot-TrEMBL)
NTSR1,NTSR2 R-HSA-388917 (Reactome)
NTSR2 ProteinO95665 (Uniprot-TrEMBL)
O-octanoyl-L-serine-GHRL-1(24-50) ProteinQ9UBU3-1 (Uniprot-TrEMBL)
O-octanoyl-L-serine-GHRL-1(24-51) ProteinQ9UBU3-1 (Uniprot-TrEMBL)
OLEA MetaboliteCHEBI:16196 (ChEBI)
OPN4 ProteinQ9UHM6 (Uniprot-TrEMBL)
OXT(20-28) ProteinP01178 (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)
PI(4,5)P2 MetaboliteCHEBI:18348 (ChEBI)
PI3K alphaComplexR-HSA-198379 (Reactome)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 ProteinO00459 (Uniprot-TrEMBL)
PIK3R3 ProteinQ92569 (Uniprot-TrEMBL)
PLC beta:G alpha (q/11)ComplexR-HSA-398158 (Reactome)
PLC-beta:G-alpha(q/11):DAG:IP3ComplexR-HSA-8983509 (Reactome)
PLC-beta:G-alpha(q/11):PIP2ComplexR-HSA-8983508 (Reactome)
PLC-betaComplexR-HSA-111854 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 ProteinQ15147 (Uniprot-TrEMBL)
PMCH(147-165) ProteinP20382 (Uniprot-TrEMBL)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
PRKCAProteinP17252 (Uniprot-TrEMBL)
PROK1 ProteinP58294 (Uniprot-TrEMBL)
PROK1,PROK2 R-HSA-444692 (Reactome)
PROK2 ProteinQ9HC23 (Uniprot-TrEMBL)
PROKR1 ProteinQ8TCW9 (Uniprot-TrEMBL)
PROKR1,PROKR2 R-HSA-444628 (Reactome)
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 kinaseComplexR-HSA-199849 (Reactome)
Photon R-ALL-419777 (Reactome)
Protein Kinase C, alpha type: DAGComplexR-HSA-422275 (Reactome)
Proteinase-activated receptors R-HSA-389458 (Reactome)
QRFP ProteinP83859 (Uniprot-TrEMBL)
QRFPR ProteinQ96P65 (Uniprot-TrEMBL)
RAF/MAP kinase cascadePathwayR-HSA-5673001 (Reactome) The RAS-RAF-MEK-ERK pathway regulates processes such as proliferation, differentiation, survival, senescence and cell motility in response to growth factors, hormones and cytokines, among others. Binding of these stimuli to receptors in the plasma membrane promotes the GEF-mediated activation of RAS at the plasma membrane and initiates the three-tiered kinase cascade of the conventional MAPK cascades. GTP-bound RAS recruits RAF (the MAPK kinase kinase), and promotes its dimerization and activation (reviewed in Cseh et al, 2014; Roskoski, 2010; McKay and Morrison, 2007; Wellbrock et al, 2004). Activated RAF phosphorylates the MAPK kinase proteins MEK1 and MEK2 (also known as MAP2K1 and MAP2K2), which in turn phophorylate the proline-directed kinases ERK1 and 2 (also known as MAPK3 and MAPK1) (reviewed in Roskoski, 2012a, b; Kryiakis and Avruch, 2012). Activated ERK proteins may undergo dimerization and have identified targets in both the nucleus and the cytosol; consistent with this, a proportion of activated ERK protein relocalizes to the nucleus in response to stimuli (reviewed in Roskoski 2012b; Turjanski et al, 2007; Plotnikov et al, 2010; Cargnello et al, 2011). Although initially seen as a linear cascade originating at the plasma membrane and culminating in the nucleus, the RAS/RAF MAPK cascade is now also known to be activated from various intracellular location. Temporal and spatial specificity of the cascade is achieved in part through the interaction of pathway components with numerous scaffolding proteins (reviewed in McKay and Morrison, 2007; Brown and Sacks, 2009).
The importance of the RAS/RAF MAPK cascade is highlighted by the fact that components of this pathway are mutated with high frequency in a large number of human cancers. Activating mutations in RAS are found in approximately one third of human cancers, while ~8% of tumors express an activated form of BRAF (Roberts and Der, 2007; Davies et al, 2002; Cantwell-Dorris et al, 2011).
RGS proteins active for G alpha (q)ComplexR-HSA-921123 (Reactome)
RGS18 ProteinQ9NS28 (Uniprot-TrEMBL)
RGS19 ProteinP49795 (Uniprot-TrEMBL)
RGS2 ProteinP41220 (Uniprot-TrEMBL)
RGS21 ProteinQ2M5E4 (Uniprot-TrEMBL)
RGS3 ProteinP49796 (Uniprot-TrEMBL)
RGSL1 ProteinA5PLK6 (Uniprot-TrEMBL)
RGZ MetaboliteCHEBI:50122 (ChEBI)
RPS6KA1 ProteinQ15418 (Uniprot-TrEMBL)
RPS6KA2 ProteinQ15349 (Uniprot-TrEMBL)
RPS6KA3 ProteinP51812 (Uniprot-TrEMBL)
Ribosomal protein S6 kinaseComplexR-HSA-199858 (Reactome)
SAA1(19-122) ProteinP0DJI8 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
TAC1(58-68) ProteinP20366 (Uniprot-TrEMBL)
TAC1(98-107) ProteinP20366 (Uniprot-TrEMBL)
TAC3 ProteinQ9UHF0 (Uniprot-TrEMBL)
TACR1 ProteinP25103 (Uniprot-TrEMBL)
TACR2 ProteinP21452 (Uniprot-TrEMBL)
TACR3 ProteinP29371 (Uniprot-TrEMBL)
TBXA2R ProteinP21731 (Uniprot-TrEMBL)
TRH R-HSA-444529 (Reactome)
TRH(114-116) ProteinP20396 (Uniprot-TrEMBL)
TRH(135-137) ProteinP20396 (Uniprot-TrEMBL)
TRH(152-154) ProteinP20396 (Uniprot-TrEMBL)
TRH(186-188) ProteinP20396 (Uniprot-TrEMBL)
TRH(227-229) ProteinP20396 (Uniprot-TrEMBL)
TRH(84-86) ProteinP20396 (Uniprot-TrEMBL)
TRHR ProteinP34981 (Uniprot-TrEMBL)
TRIO ProteinO75962 (Uniprot-TrEMBL)
TRIO family RhoGEFsComplexR-HSA-399963 (Reactome)
TXA2 MetaboliteCHEBI:15627 (ChEBI)
UDP MetaboliteCHEBI:17659 (ChEBI)
UTS2 ProteinO95399 (Uniprot-TrEMBL)
UTS2,UTS2B R-HSA-445115 (Reactome)
UTS2B ProteinQ765I0 (Uniprot-TrEMBL)
UTS2R ProteinQ9UKP6 (Uniprot-TrEMBL)
Valerate MetaboliteCHEBI:31011 (ChEBI)
XCL1 ProteinP47992 (Uniprot-TrEMBL)
XCL1,XCL2 R-HSA-373356 (Reactome)
XCL2 ProteinQ9UBD3 (Uniprot-TrEMBL)
XCR1 ProteinP46094 (Uniprot-TrEMBL)
p-4S,T231,T365-RPS6KA3 ProteinP51812 (Uniprot-TrEMBL)
p-4S,T356,T570-RPS6KA2 ProteinQ15349 (Uniprot-TrEMBL)
p-4S,T359,T573-RPS6KA1 ProteinQ15418 (Uniprot-TrEMBL)
p-6Y-EGFR ProteinP00533 (Uniprot-TrEMBL)
p-ERK1/2/5ComplexR-HSA-199878 (Reactome)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-T185,Y187-MAPK1 ProteinP28482 (Uniprot-TrEMBL)
p-T202,Y204-MAPK3 ProteinP27361 (Uniprot-TrEMBL)
p-T218,Y220-MAPK7 ProteinQ13164 (Uniprot-TrEMBL)
p21 RAS:GDPComplexR-HSA-109796 (Reactome)
p21 RAS:GTPComplexR-HSA-109783 (Reactome)
pH sensing receptors R-HSA-444736 (Reactome)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-198746 (Reactome)
ADPArrowR-HSA-199895 (Reactome)
ADRBK1R-HSA-416516 (Reactome)
ATPR-HSA-198746 (Reactome)
ATPR-HSA-199895 (Reactome)
CCKBRR-HSA-870269 (Reactome)
CREB1R-HSA-199895 (Reactome)
DAGR-HSA-400015 (Reactome)
EGFRR-HSA-2179387 (Reactome)
G-protein alpha (q):GRK2ArrowR-HSA-416516 (Reactome)
G-protein alpha (q):GRK5ArrowR-HSA-416510 (Reactome)
G-protein alpha (q/11): GTPArrowR-HSA-749452 (Reactome)
G-protein alpha (q/11): GTPR-HSA-398188 (Reactome)
G-protein alpha (q/11): GTPR-HSA-400586 (Reactome)
G-protein alpha (q/11): GTPR-HSA-416358 (Reactome)
G-protein alpha (q/11): GTPR-HSA-416510 (Reactome)
G-protein alpha (q/11): GTPR-HSA-416516 (Reactome)
G-protein alpha (q/11): GTPR-HSA-418582 (Reactome)
G-protein alpha (q/11):GDPArrowR-HSA-418582 (Reactome)
G-protein alpha (q/11):GDPR-HSA-750993 (Reactome)
G-protein alpha (q/11):PI3K alphaArrowR-HSA-416358 (Reactome)
G-protein alpha

(q/11):Trio family

RhoGEFs
ArrowR-HSA-400586 (Reactome)
G-protein alpha (q/11)mim-catalysisR-HSA-418582 (Reactome)
G-protein beta-gamma complexArrowR-HSA-749452 (Reactome)
G-protein beta-gamma complexR-HSA-750993 (Reactome)
GAST(76-92)R-HSA-870269 (Reactome)
GDPArrowR-HSA-2179407 (Reactome)
GDPArrowR-HSA-379048 (Reactome)
GPCRs that activate Gq/11ArrowR-HSA-749452 (Reactome)
GRB2-1:SOS1R-HSA-2179415 (Reactome)
GRB2:SOS1:HB-EGF:p-6Y-EGFRArrowR-HSA-2179415 (Reactome)
GRB2:SOS1:HB-EGF:p-6Y-EGFRmim-catalysisR-HSA-2179407 (Reactome)
GRK5R-HSA-416510 (Reactome)
GTPR-HSA-2179407 (Reactome)
GTPR-HSA-379048 (Reactome)
Gastrin:CCKBRArrowR-HSA-870269 (Reactome)
HB-EGF:p-6Y-EGFR dimerArrowR-HSA-2179387 (Reactome)
HB-EGF:p-6Y-EGFR dimerR-HSA-2179415 (Reactome)
HBEGF(149-208)ArrowR-HSA-2179402 (Reactome)
HBEGF(20-208)R-HSA-2179402 (Reactome)
HBEGF(20-62)ArrowR-HSA-2179402 (Reactome)
HBEGF(63-148)ArrowR-HSA-2179402 (Reactome)
HBEGF(63-148)R-HSA-2179387 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)
ArrowR-HSA-750993 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)
R-HSA-749448 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (active)
ArrowR-HSA-379048 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (active)
R-HSA-749452 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (inactive)
ArrowR-HSA-749448 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (inactive)
R-HSA-379048 (Reactome)
Ligand:GPCR

complexes that activate

Gq/11:Heterotrimeric G-protein Gq (inactive)
mim-catalysisR-HSA-379048 (Reactome)
Ligand:GPCR

complexes that

activate Gq/11
R-HSA-749448 (Reactome)
Ligands of GPCRs that activate Gq/11ArrowR-HSA-749452 (Reactome)
MMP3(100-477)ArrowR-HSA-2179413 (Reactome)
MMP3(100-477)mim-catalysisR-HSA-2179402 (Reactome)
MMP3R-HSA-2179413 (Reactome)
PI3K alphaR-HSA-416358 (Reactome)
PLC beta:G alpha (q/11)ArrowR-HSA-398188 (Reactome)
PLC beta:G alpha (q/11)mim-catalysisR-HSA-114688 (Reactome)
PLC-beta:G-alpha(q/11):DAG:IP3ArrowR-HSA-114688 (Reactome)
PLC-beta:G-alpha(q/11):PIP2R-HSA-114688 (Reactome)
PLC-betaR-HSA-398188 (Reactome)
PRKCAR-HSA-400015 (Reactome)
Phospho-Ribosomal protein S6 kinaseArrowR-HSA-198746 (Reactome)
Phospho-Ribosomal protein S6 kinasemim-catalysisR-HSA-199895 (Reactome)
Protein Kinase C, alpha type: DAGArrowR-HSA-400015 (Reactome)
Protein Kinase C, alpha type: DAGmim-catalysisR-HSA-2179413 (Reactome)
R-HSA-114688 (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.
R-HSA-198746 (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.

R-HSA-199895 (Reactome) CREB is phosphorylated at Serine 133 by RSK1/2/3.
R-HSA-2179387 (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.
R-HSA-2179402 (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).
R-HSA-2179407 (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).
R-HSA-2179413 (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.
R-HSA-2179415 (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).
R-HSA-379048 (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.
R-HSA-398188 (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.
R-HSA-400015 (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.
R-HSA-400586 (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.
R-HSA-416358 (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).
R-HSA-416510 (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.
R-HSA-416516 (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.
R-HSA-418582 (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 (Kleuss et al. 1994).
R-HSA-749448 (Reactome) Numerous functionally unrelated GPCRs couple with the Gq G-protein subtype.
R-HSA-749452 (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).
R-HSA-750993 (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.
R-HSA-870269 (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.
RGS proteins active for G alpha (q)ArrowR-HSA-418582 (Reactome)
Ribosomal protein S6 kinaseR-HSA-198746 (Reactome)
TRIO family RhoGEFsR-HSA-400586 (Reactome)
p-ERK1/2/5mim-catalysisR-HSA-198746 (Reactome)
p-S133-CREB1ArrowR-HSA-199895 (Reactome)
p21 RAS:GDPR-HSA-2179407 (Reactome)
p21 RAS:GTPArrowR-HSA-2179407 (Reactome)
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