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

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17, 47, 583411294, 3014, 425723, 3626, 534944, 463, 6, 7, 39, 5927316, 35, 48382254128, 5021cytosolnucleoplasmGTP GAST(76-92) GRM1,GRM5 CCKAR OLEA TAC1(58-68) G-protein alpha(q/11)P2RY1 TXA2 HCRTR2 NMU XCL2 OXT(20-28) RGS proteins activefor G alpha (q)PROKR2 UTS2R CHRM5 FFAR2 ligands GDP CHRM3 LTB4R2 MLN(26-47) GNAQ thrombin heavy chain F2RL3(18-385) UTS2R LPAR2 HBEGF(63-148) GNG4 ADRA1A CYSLTR1 SOS1 EDN2 LTB4R ADP RPS6KA3 PIK3R3 GNG2 GPR17 RGS19 GPR68 PIK3R2 GNG7 GCG(53-81) BRS3 EDNRB NPS ADP Hist GNA14 TACR3 LPAR6 HCRTR1 PROKR1 NMUR1 PTGFR LPAR5 EDN2 TACR2 KALRN GNG11 LPAR1,2,3,5 GNRH2(24-33) AGTR1 P2RY6 GNB2 SOS1 GPR4 GNA11 GRP(24-50) GNB4 EDNRB Ca2+ GPRC6A PMCH(147-165) G-protein alpha(q/11):PI3K alphaADR GNA14 NPFFR2 OXT(20-28) PLCB3 PLC beta:G alpha(q/11)EtCOO- or C2H5COO- LTB4R2 ATPLTC4 AGT(34-41) GNG5 LTB4R PTGFR GNA15 RPS6KA1 MCHR1 HXA HTR2A OXT(20-28) DAG FFAR2 GNG8 GRM1 CCK O-octanoyl-L-serine-GHRL-1(24-51) OLEA CYSLTR2 5HT GNA15 GNG10 HBEGF(20-208)NMUR2 GNA11 AVPR1A GAST(76-92) XCR1 AVP(20-28) O-octanoyl-L-serine-GHRL-1(24-50) GRB2-1:SOS1P2RY10 HRH1 TRHR LPAR4 HCRT(70-97) NTSR2 LPAR4 GNB1 GNA14 OPN4 TRH(114-116) SAA1(19-122) GNG7 GRB2:SOS1:HB-EGF:p-6Y-EGFRPTGER1 CCK UDP DecS-GHRL-1(24-50) Valerate NAd F2RL3(18-385) HCRT(34-66) PLCB3 GNGT2 GCG(53-81) PGE2 GNAQ UTS2B NTSR1 GNG13 ADRA1A,B,D HRH1 GPRC6A TRH(84-86) TRH(186-188) NMUR2 GNRH2(24-33) NPS LTB4 GNA11 GNRH1(24-33) NTSR1 GNG12 XCR1 TRH(227-229) GPRC6A ligands ATP Bradykinin receptor GNA15 F2RL2(22-374) TBXA2R LXA4 CH3COO- p-T202,Y204-MAPK3 TRIO DecS-GHRL-1(24-50) Protein Kinase C,alpha type: DAGTACR3 UDP GPR4 PLCB1 GnRH receptor NTSR2 HXA NPFFR1 GNA11 p-4S,T356,T570-RPS6KA2 GDPF2RL1(37-397) UTS2B NMS CH3COO- PIK3R1 p-4S,T231,T365-RPS6KA3 MLNR MMP3EtCOO- or C2H5COO- GNAQ CASR PRKCAGNG3 Valerate HCRTR1 TACR3 PTAFR GNAQ PALM GPRC6A Acyl Ghrelin TRH(135-137) BDKRB2 thrombin light chain KISS1R Pentadecanoic acid GRM1 NTSR2 G-protein alpha(q/11): GTPGNA11 Gastrin:CCKBRTAC1(58-68) PTGFR OXTR HTR2A G-protein beta-gammacomplexFPR2 CCKBR ADP OLEA PROKR2 LTD4 PGE2 FFAR3 ligands thrombin heavy chain XCL2 PLCB4 BUT PROKR1 RGZ HCRTR2 GNA15 BDKRB1 DecS-GHRL-1(24-51) FPR2 LPAR5 pH sensing receptors AVPR1B G-protein alpha(q/11):GDPLigand:GPCRcomplexesthatactivateGq/11:Heterotrimeric G-protein Gq (inactive)PLCB1 P2RY11 Basic L-amino acids GNB5 ADR, NAd TRH(186-188) PROK2 CHRM5 F2RL2(22-374) NMB(47-56) GNRHR2 BDKRB2 p21 RAS:GTPGCGR GRM5 GTP RAF/MAP kinasecascadePROK1 GNRH1(24-33) AGTR1 QRFP NMS thrombin heavy chain FFAR1 ADR EDNRA PROKR2 Ca2+ GPR65 TAC3 LPAR3 OPN4 HTR2B GTP GNA15 GRK5TRIO GDP GNRHR KISS1R GRP(24-50) HBEGF(63-148)RGZ P2RY10 TRH(114-116) GNA11 GAST(76-92) DAG TAC1(98-107) FFAR3 CCKAR OXTR TACR3 Bradykinin O-octanoyl-L-serine-GHRL-1(24-50) HCRT(34-66) AGTR1 GNG12 L-Glu DecS-GHRL-1(24-51) PLCB2 APP(672-713) HCOOH LTB4R,LTB4R2 TACR2 GNB1 PIK3CA Ca2+ P2RY2 PGF2a DDCX CCKBR TACR1 NMU GNG4 GNB4 GNG3 MT-RNR2 GNB2 p-T185,Y187-MAPK1 FFAR2 GNG13 PAF GNA14 LPAR3 GNG3 NPFFR2 GNB5 Photon MLN(26-47) TRH(84-86) GRPR P2RY1 P2RY1 GRB2-1 GAST(76-92) GPCRs that activateGq/11H+ GNG5 EDNRB TACR1 CCK GNRHR LPAR6 QRFPR PLCB3 ANXA1 TAC1(58-68) NMUR2 Basic L-amino acids LPA AGT(34-41) FFAR1 PTGER1 RGZ GNA11 UTS2 NRAS MCHR1 p-S133-CREB1GRK5 ADRA1B GNA15 OXTR TAC3 GNB3 P2RY1 TBXA2R MLNR GNRH2(24-33) TAC1(58-68) CHRM5 PIK3R1 GNAQ GNG13 CCKBR thrombin heavy chain ANXA1 CHRM1 PRKCA BRS3 GNAQ GNAQ HCRTR2 PLCB2 EDNRA CHRM1 HRAS GRM1 GHSR PTGER1 GDP GAST(76-92) GNB4 XCL1 LPAR1 PTGER1 TRH(135-137) ARHGEF25 P2RY6 NMU HCRT(70-97) KISS1R GNG13 APP(672-713) GNAQ PTAFR GNG2 P2RY2 BUT MCHR1 GNA11 GNB3 GCGR H+ HCRTR2 MCHR1,MCHR2 HXA ATP ADRBK1 PTAFR XCL1 TRHR PGF2a TAC1(98-107) NMBR GNGT1 AVPR1A PLCB2 ADPF2RL2(22-374) CCL23-2 PROK1 FFAR2 TRH(84-86) ADP Effects of PIP2hydrolysisCCKBRG-protein alpha(q/11):Trio familyRhoGEFsPAF TRHR HBEGF(20-62)GNRH ligands TAC3 GPR65 CCKAR FFAR1 ligands NTSR1,NTSR2 Ribosomal protein S6kinaseQRFP LTE4 HCRT(34-66) UTS2,UTS2B L-Glu GNGT1 BRS3 HCRT(34-66) DAGGNA14 PGE2 LPAR6 GRM5 TBXA2R PGF2a EDN1 ANXA1 NPSR1 LTB4 LPAR5 GHSR GNG10 GRPR GCGR Endothelin GNA14 GNAQ O-octanoyl-L-serine-GHRL-1(24-51) CHRM3 LTC4 CH3COO- GNA14 OPN4 FFAR2 p-6Y-EGFR GTP GNA14 HCRTR1 GNB5 LPAR6 5HT PROK2 GTPBDKRB2 NMUR1,NMUR2 GNGT2 GNG7 CCKBR UTS2R CASR Hist GNA11 P2RY10 FPR2 GNB1 UTS2B GNA14 HCOOH EDN1 GNG10 GNG5 LPAR4 MLN(26-47) LPA EDN3(97-117) GNG8 Proteinase-activated receptors PGE2 QRFPR LPAR3 GNRHR2 CHRM1 CYSLTR1,CYSLTR2 GNA15 KRAS EtCOO- or C2H5COO- Bombesin-like peptide NPS UTS2 HRH1 OXTR EDNRA L-Glu ADRBK1NMB(47-56) NPSR1 PROKR1,PROKR2 ADPPhoton QRFPR GNA15 GDPGTP MMP3(100-477)GNRH1(24-33) NTS(151-163) GTP GRP(24-50) GNB2 GAST(76-92)UTS2 ADRA1D GPR17 MT-RNR2 PROK2 OXT(20-28) RGS3 GNA15 GNA14 AcCho DDCX F2RL1(37-397) Ligand:GPCRcomplexes thatactivate Gq/11HTR2B QRFPR F2R(27-425) PAF TAC1(98-107) GNRHR2 NPFFR1,NPFFR2 Bombesin-like receptor KRAS LXA4 FFAR3 CASR NAd KISS1(68-121) GNG10 Ligand:GPCRcomplexesthatactivateGq/11:Heterotrimeric G-protein Gq (active)p-6Y-EGFR Bradykinin LTD4 G-protein alpha(q):GRK2PTGFR NAd CASR F2RL1(37-397) GTPGNGT1 Photon TACR1 LPAR4 GTP TBXA2R GNB3 P2RY11 AVP(20-28) NTS(151-163) CHRM1, 3, 5 PTAFR O-octanoyl-L-serine-GHRL-1(24-50) LPAR1 HTR2A-C GNGT1 LTD4 GNA15 PI(4,5)P2 P2RY10 TRH(135-137) GNG12 GNG4 P2RY11 ADRA1D RGS21 GPR4 GNB3 Ligands of GPCRsthat activate Gq/11GNG4 RPS6KA2 QRFP NPFFR1 HCRTR1 ADRA1B Hist LPAR2 PALM TRH(227-229) UTS2R thrombin light chain HTR2C LPA Bradykinin MLNR GPRC6A EDNRA,EDNRB PLCB3 F2R(27-425) HeterotrimericG-protein Gq/11(inactive)G-protein alpha(q):GRK5CCKAR,CCKBR AGTR1 O-octanoyl-L-serine-GHRL-1(24-51) Pentadecanoic acid GTP ARHGEF25 HBEGF(63-148) OPN4 TACR2 GPR17 BDKRB1 HTR2B RGS18 PROKR1 KISS1(68-121) XCL2 Cysteinyl leukotrienes GPR132 I(1,4,5)P3 HCOOH GPR65 PLC-beta:G-alpha(q/11):DAG:IP3UDP LTE4 NPS AVP(20-28) GNA14 GNA15 thrombin light chain GNA11 p21 RAS:GDPMCHR2 GCG(53-81) GNA11 XCR1 P2RY6 PIK3R3 GRM5 GNA11 P2RY2 NPFFR1 NTSR1 NTS(151-163) PLCB1 PROK1 EDN3(97-117) Pentadecanoic acid HBEGF(149-208)F2R(27-425) CREB1KISS1(68-121) NRAS ADRA1D TXA2 H+ PMCH(147-165) L-Glu H+ NPSR1 GPR132 TAC1(98-107) I(1,4,5)P3GNG2 GNG8 KISS1R APP(672-713) LPAR2 LPAR1 NPFF(69-76) GNAQ PI3K alphaCYSLTR2 PLCB1 HTR2C NMUR1 CYSLTR1 GNG11 GRPR LTB4 LTB4R BDKRB1 TRH(152-154) P2RY6 GNAQ NMUR1 HB-EGF:p-6Y-EGFRdimerAcCho RGS2 ADRA1B GTP LXA4 NMU HCRT(70-97) PMCH(147-165) AVP(20-28) PALM PLCB4 GPR17 ATP EDN1 GNG5 UDP CCL23-2 P2RY11 AVPR1B MT-RNR2 Ca2+ AVPR1A NTS(151-163) FFAR1 KALRN GRB2-1 GHSR EDN3(97-117) SAA1(19-122) LPA DecS-GHRL-1(24-50) NPFF(69-76) AcCho NMB(47-56) CCKBR GNG2 ADR TAC3 AGT(34-41) PGF2a MLNR TRH(227-229) PROK1,PROK2 ATPXCL1 GNG12 NMBR CYSLTR1 GPR68 MCHR2 GNG7 NMUR2 GTP AGT(34-41) GNG11 DDCX PMCH(147-165) GNA11 PLCB4 MLN(26-47) FFAR1 PLC-beta:G-alpha(q/11):PIP2Phospho-Ribosomalprotein S6 kinaseCYSLTR2 NPFF(69-76) GNB4 NPSR1 TACR2 PLCB2 CCK GDP Hist F2RL3(18-385) RGSL1 HRAS FPR2 GNG8 TRH(152-154) GNG3 TRH TXA2 HTR2C Valerate HRH1 PLCB4 CHRM3 EDN2 TACR1 GNA15 NMS LTB4R2 TRHR P2RY2 GNB2 GNGT2 Basic L-amino acids GNG11 NPFF(69-76) KISS1(68-121) GNB1 TXA2 NMBR EGFRGPR68 p-T218,Y220-MAPK7 HCRT(70-97) ADRA1A AcCho LTC4 NMS GNRHR CCL23-2 HTR2A SAA1(19-122) DecS-GHRL-1(24-51) GNA14 PLC-betaADRA1A PIK3R2 XCR1 FFAR3 p-ERK1/2/5Photon GNGT2 MCHR2 GCGR NPFFR2 PAF XCL1,XCL2 TRH(114-116) Bradykinin GHSR LTB4 GPR132 BUT TRIO family RhoGEFs5HT QRFP AVPR1A,B GNA15 TRH(152-154) GNB5 GCG(53-81) thrombin light chain GNAQ PIK3CA p-4S,T359,T573-RPS6KA1 LTE4 FFAR3 GNA14 TRH(186-188) ATP AVPR1B GNAQ 5HT FPR2 ligands 10, 1355, 563155, 568, 9, 33, 5115, 4555, 5655, 56311, 2, 12, 18-20, 24...55, 5655, 5655, 5655, 56


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

View all...
  1. Reuben PM, Brogley MA, Sun Y, Cheung HS.; ''Molecular mechanism of the induction of metalloproteinases 1 and 3 in human fibroblasts by basic calcium phosphate crystals. Role of calcium-dependent protein kinase C alpha.''; PubMed Europe PMC Scholia
  2. Elenius K, Paul S, Allison G, Sun J, Klagsbrun M.; ''Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation.''; PubMed Europe PMC Scholia
  3. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
  4. Wank SA.; ''Cholecystokinin receptors.''; PubMed Europe PMC Scholia
  5. Grabowska AM, Watson SA.; ''Role of gastrin peptides in carcinogenesis.''; PubMed Europe PMC Scholia
  6. Tanimura A, Nezu A, Morita T, Hashimoto N, Tojyo Y.; ''Interplay between calcium, diacylglycerol, and phosphorylation in the spatial and temporal regulation of PKCalpha-GFP.''; PubMed Europe PMC Scholia
  7. Ranganathan A, Pearson GW, Chrestensen CA, Sturgill TW, Cobb MH.; ''The MAP kinase ERK5 binds to and phosphorylates p90 RSK.''; PubMed Europe PMC Scholia
  8. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T.; ''Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells.''; PubMed Europe PMC Scholia
  9. Okutani T, Okabayashi Y, Kido Y, Sugimoto Y, Sakaguchi K, Matuoka K, Takenawa T, Kasuga M.; ''Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells.''; PubMed Europe PMC Scholia
  10. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  11. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  12. De Cesare D, Jacquot S, Hanauer A, Sassone-Corsi P.; ''Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription of c-fos gene.''; PubMed Europe PMC Scholia
  13. de Weerth A, Bläker M, von Schrenck T.; ''[Receptors for cholecystokinin and gastrin]''; PubMed Europe PMC Scholia
  14. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  15. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D.; ''Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.''; PubMed Europe PMC Scholia
  16. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
  17. Roux PP, Richards SA, Blenis J.; ''Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.''; PubMed Europe PMC Scholia
  18. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
  19. Mizuno N, Itoh H.; ''Functions and regulatory mechanisms of Gq-signaling pathways.''; PubMed Europe PMC Scholia
  20. Suzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M.; ''Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site.''; PubMed Europe PMC Scholia
  21. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
  22. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
  23. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  24. Gilon P, Henquin JC.; ''Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function.''; PubMed Europe PMC Scholia
  25. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  26. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  27. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  28. Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M.; ''A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF.''; PubMed Europe PMC Scholia
  29. Batzer AG, Rotin D, Ureña JM, Skolnik EY, Schlessinger J.; ''Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
  30. Ito M, Matsui T, Taniguchi T, Tsukamoto T, Murayama T, Arima N, Nakata H, Chiba T, Chihara K.; ''Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin.''; PubMed Europe PMC Scholia
  31. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  32. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  33. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia

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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