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

From WikiPathways

Revision as of 10:41, 10 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
8, 17, 19205364, 2328, 37392533, 382, 313, 143518262111, 22, 29, 36, 41126, 279124UTS2RUrotensin 2, 2B Proteinase-activated receptors LigandGPCR complexes that activate Gq/11 pH sensing receptors XC1 ligands ThrombinProteinase-activated receptors Ligands of FFAR1 Motilin receptorMotilin NeurotensinNeurotensin receptor Acyl ghrelinGHSR Alpha-1 adrenoceptor Acyl ghrelinGHSR HB-EGFp-6Y-EGFR PI3K alpha G-protein beta-gamma complex GastrinCCKBR Group I Metabotropic glutamate receptors Orexin 2 receptorOrexin B GNRH ligands P2RY9LPA Melanin-concentrating hormone receptors G-protein alpha p21 RAS LigandGPCR complexes that activate Gq/11 Group I Metabotropic glutamate receptorsGlu PAF receptorPAF 5-HT2 receptor G-protein alpha HRH1Histamine TP receptorThromboxane A2 P2RY6UDP Prokineticin receptorsprokineticin Bradykinin receptor Prokineticin receptors Cholecystokinin receptors LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq Cysteinyl leukotriene receptors CASRCalcium Type 1 angiotensin II receptorAngiotensin II G-protein alpha Bombesin-like receptorbombesin-like peptide LTB4 receptors Orexin 2 receptorOrexin B G-protein alpha G-protein alpha CHRM1, 3, 5 FPRL1 ligands G-protein alpha Neuromedin K receptorNeurokinin B peptide Group I Metabotropic glutamate receptors Cysteinyl leukotriene receptorsCysteinyl leukotrienes Ligands of FFAR1 pH sensing receptors GnRH receptorGNRH ligands LPA-binding EDG receptors Basic L-amino acids G-protein alpha P2RY11 ATP LPA-binding EDG receptors LPA CASRCalcium NPSNPSR Alpha-1 adrenoceptorCatecholamine Substance P receptorSubstance P peptide Basic L-amino acids GPRC6A ligands Vasopressin receptor type 1AVP Urotensin 2, 2B Cysteinyl leukotrienes M1/M3/M5acetylcholine Prokineticin receptorsprokineticin OxytocinOxytocin receptor Heterotrimeric G-protein Gq EndothelinEndothelin receptor Alpha-1 adrenoceptor GRB2SOS1 EP1 receptorPGE2 LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq P2RY10LPA TRH Substance K receptorNeurokinin A peptide G-protein beta-gamma complex Neuromedin-SNeuromedin-U receptor 2 Carboxylate ligands of FFAR2 HRH1Histamine LPA-binding EDG receptors LPA MetastinKiSS1R Endothelin receptor P2RY5LPA 5-HT2 receptorSerotonin LTB4 receptors Catecholamine CCKCholecystokinin receptors GNRH ligands Substance P receptorSubstance P peptide Acyl Ghrelin GPR17UDP Neuromedin K receptorNeurokinin B peptide GastrinCCKBR FPRL1 ligands Endothelin FFAR1fatty acid Endothelin receptor GPRC6A ligands Vasopressin receptor type 1AVP HB-EGFp-6Y-EGFR P2RY1ADP Type 1 angiotensin II receptorAngiotensin II FFAR1fatty acid Urotensin 2, 2B Neuromedin-SNeuromedin-U receptor 2 FFAR2Carboxylate ligands G-protein alpha Neuropeptide FF receptorNeuropeptide FF Neuromedin-U receptors LTB4 receptorsLTB4 GPR17UDP Neuromedin-UNeuromedin receptors LPA-binding EDG receptors OxytocinOxytocin receptor Activated thrombin Bombesin-like peptide G-protein beta-gamma complex HB-EGFp-6Y-EGFR dimer Group I Metabotropic glutamate receptorsGlu QRFP receptorQRFP XC1 ligands G-protein alpha EndothelinEndothelin receptor Carboxylate ligands of FFAR2 Neuromedin-UNeuromedin receptors FPRL1FPRL1 ligands TRHTRHR P2RY2ATP P2RY11 ATP p21 RASGTP P2RY1ADP GRB2SOS1 Carboxylate ligands of FFAR3 G-protein alpha Neuromedin-U receptors TRH GPRC6A receptorGPRC6A ligands Neuropeptide FF receptor ThrombinProteinase-activated receptors GastrinCCKBR P2RY9LPA PLC betaG alpha NPSNPSR cytosolNeurotensinNeurotensin receptor TRIO family RhoGEFs Vasopressin receptor type 1 G-protein alpha Neuropeptide FF receptorNeuropeptide FF GnRH receptor M1/M3/M5acetylcholine FFAR3Carboxylate ligands PAF receptorPAF Proteinase-activated receptors G-protein alpha Motilin receptorMotilin Prokineticin Melanospinphoton G-protein alpha pH sensing receptorsH+ Activated thrombin Chemokine XC receptor 1 XC1 ligands nucleoplasmFFAR2Carboxylate ligands TRHTRHR G-protein alpha G-protein alpha G-protein alpha G-protein alpha P2RY6UDP CHRM1, 3, 5 Heterotrimeric G-protein Gq/11 FPRL1FPRL1 ligands Protein Kinase C, alpha type DAG Cysteinyl leukotriene receptorsCysteinyl leukotrienes Cysteinyl leukotrienes Neuropeptide FF receptor G-protein alpha Heterotrimeric G-protein Gq/11 GlucagonGCGR Bombesin-like receptorbombesin-like peptide GRB2SOS1HB-EGFp-6Y-EGFR Bradykinin receptorBradykinin EP1 receptorPGE2 MCHMelanin-concentrating hormone receptors MetastinKiSS1R PI3K alpha Catecholamine G-protein alpha Neurotensin receptor Carboxylate ligands of FFAR3 PLC-beta G-protein alpha UTS2RUrotensin 2, 2B pH sensing receptorsH+ HB-EGFp-6Y-EGFR dimer p21 RASGDP CCKCholecystokinin receptors G-protein alpha Cholecystokinin receptors p21 RAS 5-HT2 receptor GPRC6A receptorGPRC6A ligands GnRH receptorGNRH ligands LTB4 receptorsLTB4 Orexin 1 receptorOrexin A Cysteinyl leukotriene receptors G-protein beta-gamma complex G-protein alpha QRFP receptorQRFP G-protein alpha P2RY2ATP Endothelin Bradykinin receptor GlucagonGCGR Acyl Ghrelin FFAR3Carboxylate ligands P2RY10LPA Neurotensin receptor Prokineticin receptors P2RY5LPA MCHMelanin-concentrating hormone receptors Orexin 1 receptorOrexin A FP receptorPGF2-alpha Alpha-1 adrenoceptorCatecholamine Substance K receptorNeurokinin A peptide Prokineticin Melanin-concentrating hormone receptors TP receptorThromboxane A2 Melanospinphoton Bradykinin receptorBradykinin Vasopressin receptor type 1 Bombesin-like peptide GnRH receptor FP receptorPGF2-alpha 5-HT2 receptorSerotonin Chemokine XC receptor 1 XC1 ligands G-protein alpha PLCB1 GNAQ 5HT CYSLTR2 GNA11 P2RY2 Glucagon O-octanoyl-L-serine-GHRL-1GNRHR2GNAQ GTP ADPGNAQ HCRTR1 LPAR6 LTD4 LTB4R Bradykinin GASTGlucagon NMUR1 ANXA1 AcCho KALRN AGTMCHR2 PTGFR OPN4 Substance P peptide NMUR2 H+ HTR2B HBEGFF2RMCHR1 L-Lys F2RL2GNA14 XCL2 GDPPLCB3GNA11 Glu GDP KISS1R G-protein alpha FPR2 Substance P peptide GPRC6A ADRA1D PLC-betaADRA1B EGFRTRHGTP ADRBK1UTS2R GNA14 AcCho UTS2PAF GASTLigandGPCR complexes that activate Gq/11FFAR2 PLCB4 CYSLTR1 TRHP2RY1 HRH1 GNA11 GTPMLNGASTPALM TRHTRHp-S133-CREB1Effects of PIP2 hydrolysisGNRHR PTGFR HCRTR2 AVPR1B HXA HTR2B NPSR1 LPAR3 PLCB2 GCGR CHRM3 F2RL3NPFFR1 MT-RNR2GHSR GRB2-1 TAC3CH3COO- NPFFR2 EDN1GPR17 Ligands of GPCRs that activate Gq/11GNA15 UDP CYSLTR2 GNA14 GNAQ MMP3CCKAR LXA4 LTC4 CH3COO- GTP SOS1 EDN3ADRA1D SAA1OXTR ARHGEF25 Ca2+ SOS1 P2RY11 F2RTRHP2RY2 ATPKISS1R GTP GPR65 G-protein alpha p21 RASGDPBDKRB1 ADP CASR GPR4 LTE4 Valerate GRK5 PLC betaG alpha OLEA G-protein alpha GPR17 TRHGNA11 PGF2a TRHNMUR1 CCK PROK2 GNAQ OXTGNRHR NMUR2 O-octanoyl-L-serine-GHRL-1LTB4 LPAR6 HBEGFHCRTGNA15 GPR132 UTS2BBDKRB2 NPFFFFAR2 NPFFNRAS HCRTR1 AVPR1A CHRM1 GNA15 PGE2 ADP TRHLigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq GRPLPAR3 KISS1PIUTS2BL-Arg GNA15 AVPR1B Phospho-Ribosomal protein S6 kinasethrombin light chain NMUHRASNPSR1 OXTR GPR65 NMBBDKRB2 GDPGRB2-1 L-Orn RAF/MAP kinase cascadeDAGADRA1A FFAR1 TBXA2ROPN4 Ribosomal protein S6 kinaseTACR2 CCK KRASQRFPLTE4 BUT EDN2GNA11 PROKR1 Ca2+ TRHMLNR thrombin heavy chain GRB2SOS1EtCOO- or C2H5COO- MCHR2 LPAR5 ANXA1 GNA14 NTSGPRC6A MT-RNR2thrombin heavy chain LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq FFAR1 ADRA1A Neurokinin A peptide LTB4R BUT DecS-GHRL-1GNA14 OLEA GDP HCOOH HTR2A O-octanoyl-L-serine-GHRL-1TRIO Pentadecanoic acid EDNRB LTB4R2 XCL1 KISS1MLNRGZ GNA15 LPAR4 HTR2CGPR68 EDN3GPR4 XCL2 NMBPROKR2 CREB1GNAQ EDN2HXA L-Lys GRM1 PGF2a GRM1 GNA11 AGTR1 NTSR2 P2RY11 EDN1p-ERK1/2/5PMCHTACR1 NTSR2 L-Arg QRFPQRFPR GNRH1PROKR1 ATPCCKBR GNA11 PROK1 PI3K alphaProtein Kinase C, alpha type DAGATP NTSR1 CCKAR LPAR4 ADR PAF O-octanoyl-L-serine-GHRL-1NTSUDP KRASF2RL1GNA11 ADRA1B NAd MLNR CHRM5 XCL1 Pentadecanoic acid OXTP2RY6 NMSTXA2 LPAR1 UTS2ADR G-protein alpha GDP HTR2A F2RL1GNAQ HRASp-6Y-EGFR GNA14 NPFFR1 PROKR2 TAC3PTGER1 FFAR3 G-protein beta-gamma complexPTAFR NMSCCKBRPRKCA HBEGFNPFFR2 Valerate NAd GNA15 LTC4 LPAR2 HB-EGFp-6Y-EGFR dimerGPCRs that activate Gq/11GRK5P2RY1 Hist GASTGTP CHRM5 AVPLPAR2 GNRH2P2RY10 TRIO family RhoGEFsUTS2R NPSRGZ G-protein alpha TBXA2Rp21 RASGTPGNAQ TACR3 ADPAGTR1 5HT HCRTCCKBR BDKRB1 HBEGFTACR3 GRM5 DecS-GHRL-1HCRTTRHR G-protein alpha GNRHR2GRPFPR2 IAVPR1A GNAQ MCHR1 Neurokinin A peptide Heterotrimeric G-protein Gq/11 HBEGFDDCX GNA11 F2RL2Glu GTPTXA2 TACR2 LTB4R2 G-protein alpha GNA15 GRB2SOS1HB-EGFp-6Y-EGFRPROK2 NPSLXA4 GNA14 GNA15 GNA14 QRFPR LPAR1 GNA14 GRM5 ADRBK1PRKCACCL23-2 TRHPTGER1 H+ APPGCGR GastrinCCKBRGNRH2GPR132 RGS proteins active for G alpha LTD4 P2RY10 HCRTR2 LPA LTB4 CHRM3 Bradykinin GPR68 EDNRA PTAFR DecS-GHRL-1EtCOO- or C2H5COO- GDP L-Orn AVPPMCHPALM HCOOH TACR1 HRH1 GNAQ Hist CYSLTR1 XCR1 GHSR LPA TRHTRHR GTP NRAS CCKBR DecS-GHRL-1APPP2RY6 LPAR5 CCL23-2 TRHGNA14 GNA15 CASR HCRTPIK3CA CHRM1 NTSR1 PGE2 GNRH1DAG EDNRA GTP ATP AGTDDCX NMUPIK3CA FFAR3 HBEGFthrombin light chain XCR1 F2RL3p-6Y-EGFR GNA15 GNA11 SAA1HTR2CEDNRB GTP PROK1 30, 31, 347, 1516, 4016, 4016, 4016, 4010, 32


Description

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

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

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

View all...
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)
ADRA1A ProteinP35348 (Uniprot-TrEMBL)
ADRA1B ProteinP35368 (Uniprot-TrEMBL)
ADRA1D ProteinP25100 (Uniprot-TrEMBL)
ADRBK1ProteinP25098 (Uniprot-TrEMBL)
AGTProteinP01019 (Uniprot-TrEMBL)
AGTR1 ProteinP30556 (Uniprot-TrEMBL)
ANXA1 ProteinP04083 (Uniprot-TrEMBL)
APPProteinP05067 (Uniprot-TrEMBL)
ARHGEF25 ProteinQ86VW2 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
AVPProteinP01185 (Uniprot-TrEMBL)
AVPR1A ProteinP37288 (Uniprot-TrEMBL)
AVPR1B ProteinP47901 (Uniprot-TrEMBL)
AcCho MetaboliteCHEBI:15355 (ChEBI)
BDKRB1 ProteinP46663 (Uniprot-TrEMBL)
BDKRB2 ProteinP30411 (Uniprot-TrEMBL)
BUT MetaboliteCHEBI:30772 (ChEBI)
Bradykinin ProteinP01042 (Uniprot-TrEMBL)
CASR ProteinP41180 (Uniprot-TrEMBL)
CCK ProteinP06307 (Uniprot-TrEMBL)
CCKAR ProteinP32238 (Uniprot-TrEMBL)
CCKBR ProteinP32239 (Uniprot-TrEMBL)
CCKBRProteinP32239 (Uniprot-TrEMBL)
CCL23-2 ProteinP55773-2 (Uniprot-TrEMBL)
CH3COO- MetaboliteCHEBI:15366 (ChEBI)
CHRM1 ProteinP11229 (Uniprot-TrEMBL)
CHRM3 ProteinP20309 (Uniprot-TrEMBL)
CHRM5 ProteinP08912 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
CYSLTR1 ProteinQ9Y271 (Uniprot-TrEMBL)
CYSLTR2 ProteinQ9NS75 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
DDCX MetaboliteCHEBI:30805 (ChEBI)
DecS-GHRL-1ProteinQ9UBU3-1 (Uniprot-TrEMBL)
EDN1ProteinP05305 (Uniprot-TrEMBL)
EDN2ProteinP20800 (Uniprot-TrEMBL)
EDN3ProteinP14138 (Uniprot-TrEMBL)
EDNRA ProteinP25101 (Uniprot-TrEMBL)
EDNRB ProteinP24530 (Uniprot-TrEMBL)
EGFRProteinP00533 (Uniprot-TrEMBL)
Effects of PIP2 hydrolysisPathwayWP1809 (WikiPathways) Hydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by phospholipase C (PLC) produces diacylglycerol (DAG) and inositol triphosphate (IP3). Both are potent second messengers. IP3 diffuses into the cytosol, but as DAG is a hydrophobic lipid it remains within the plasma membrane. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, while DAG activates the conventional and unconventional protein kinase C (PKC) isoforms, facilitating the translocation of PKC from the cytosol to the plasma membrane. The effects of DAG are mimicked by tumor-promoting phorbol esters. DAG is also a precursor for the biosynthesis of prostaglandins, the endocannabinoid 2-arachidonoylglycerol and an activator of a subfamily of TRP-C (Transient Receptor Potential Canonical) cation channels 3, 6, and 7.
EtCOO- or C2H5COO- MetaboliteCHEBI:30768 (ChEBI)
F2RL1ProteinP55085 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RL2ProteinO00254 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RL3ProteinQ96RI0 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
F2RProteinP25116 (Uniprot-TrEMBL) This is the inactive form of the receptor, before protease activation. Proteinase (protease) activated receptors are activated by the cleavage of an N-terminal extracellular segment by serine proteases, particularly thrombin which activates PAR1, 3 and 4. The cleaved fragment is an activating ligand for the receptor; synthetic peptide mimics of the N-terminal fragment can activate uncleaved receptors.
FFAR1 ProteinO14842 (Uniprot-TrEMBL)
FFAR2 ProteinO15552 (Uniprot-TrEMBL)
FFAR3 ProteinO14843 (Uniprot-TrEMBL)
FPR2 ProteinP25090 (Uniprot-TrEMBL)
G-protein alpha ProteinREACT_18229 (Reactome)
G-protein alpha ComplexREACT_19587 (Reactome)
G-protein alpha ComplexREACT_19592 (Reactome)
G-protein alpha ComplexREACT_19870 (Reactome)
G-protein alpha ComplexREACT_20202 (Reactome)
G-protein alpha ComplexREACT_3769 (Reactome)
G-protein alpha ComplexREACT_5863 (Reactome)
G-protein beta-gamma complexComplexREACT_15674 (Reactome)
GASTProteinP01350 (Uniprot-TrEMBL)
GCGR ProteinP47871 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GHSR ProteinQ92847 (Uniprot-TrEMBL)
GNA11 ProteinP29992 (Uniprot-TrEMBL)
GNA14 ProteinO95837 (Uniprot-TrEMBL)
GNA15 ProteinP30679 (Uniprot-TrEMBL)
GNAQ ProteinP50148 (Uniprot-TrEMBL)
GNRH1ProteinP01148 (Uniprot-TrEMBL)
GNRH2ProteinO43555 (Uniprot-TrEMBL)
GNRHR ProteinP30968 (Uniprot-TrEMBL)
GNRHR2ProteinQ96P88 (Uniprot-TrEMBL)
GPCRs that activate Gq/11ProteinREACT_22567 (Reactome)
GPR132 ProteinQ9UNW8 (Uniprot-TrEMBL)
GPR17 ProteinQ13304 (Uniprot-TrEMBL)
GPR4 ProteinP46093 (Uniprot-TrEMBL)
GPR65 ProteinQ8IYL9 (Uniprot-TrEMBL)
GPR68 ProteinQ15743 (Uniprot-TrEMBL)
GPRC6A ProteinQ5T6X5 (Uniprot-TrEMBL)
GRB2

SOS1 HB-EGF

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

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ComplexREACT_22589 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ComplexREACT_22865 (Reactome)
Ligand GPCR complexes that activate Gq/11ComplexREACT_18247 (Reactome)
Ligands of GPCRs that activate Gq/11MetaboliteREACT_23264 (Reactome)
MCHR1 ProteinQ99705 (Uniprot-TrEMBL)
MCHR2 ProteinQ969V1 (Uniprot-TrEMBL)
MLNProteinP12872 (Uniprot-TrEMBL)
MLNR ProteinO43193 (Uniprot-TrEMBL)
MMP3ProteinP08254 (Uniprot-TrEMBL)
MT-RNR2ProteinQ8IVG9 (Uniprot-TrEMBL)
NAd MetaboliteCHEBI:18357 (ChEBI)
NMBProteinP08949 (Uniprot-TrEMBL)
NMSProteinQ5H8A3 (Uniprot-TrEMBL)
NMUProteinP48645 (Uniprot-TrEMBL)
NMUR1 ProteinQ9HB89 (Uniprot-TrEMBL)
NMUR2 ProteinQ9GZQ4 (Uniprot-TrEMBL)
NPFFProteinO15130 (Uniprot-TrEMBL)
NPFFR1 ProteinQ9GZQ6 (Uniprot-TrEMBL)
NPFFR2 ProteinQ9Y5X5 (Uniprot-TrEMBL)
NPSProteinP0C0P6 (Uniprot-TrEMBL)
NPSR1 ProteinQ6W5P4 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
NTSProteinP30990 (Uniprot-TrEMBL)
NTSR1 ProteinP30989 (Uniprot-TrEMBL)
NTSR2 ProteinO95665 (Uniprot-TrEMBL)
Neurokinin A peptide ProteinP20366 (Uniprot-TrEMBL)
O-octanoyl-L-serine-GHRL-1ProteinQ9UBU3-1 (Uniprot-TrEMBL)
OLEA MetaboliteCHEBI:16196 (ChEBI)
OPN4 ProteinQ9UHM6 (Uniprot-TrEMBL)
OXTProteinP01178 (Uniprot-TrEMBL)
OXTR ProteinP30559 (Uniprot-TrEMBL)
P2RY1 ProteinP47900 (Uniprot-TrEMBL)
P2RY10 ProteinO00398 (Uniprot-TrEMBL)
P2RY11 ProteinQ96G91 (Uniprot-TrEMBL)
P2RY2 ProteinP41231 (Uniprot-TrEMBL)
P2RY6 ProteinQ15077 (Uniprot-TrEMBL)
PAF MetaboliteCHEBI:52450 (ChEBI)
PALM MetaboliteCHEBI:15756 (ChEBI)
PGE2 MetaboliteCHEBI:15551 (ChEBI)
PGF2a MetaboliteCHEBI:15553 (ChEBI)
PI3K alphaComplexREACT_12697 (Reactome)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PLC beta G alpha ComplexREACT_17363 (Reactome)
PLC-betaProteinREACT_15673 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 ProteinQ15147 (Uniprot-TrEMBL)
PMCHProteinP20382 (Uniprot-TrEMBL)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
PRKCAProteinP17252 (Uniprot-TrEMBL)
PROK1 ProteinP58294 (Uniprot-TrEMBL)
PROK2 ProteinQ9HC23 (Uniprot-TrEMBL)
PROKR1 ProteinQ8TCW9 (Uniprot-TrEMBL)
PROKR2 ProteinQ8NFJ6 (Uniprot-TrEMBL)
PTAFR ProteinP25105 (Uniprot-TrEMBL)
PTGER1 ProteinP34995 (Uniprot-TrEMBL)
PTGFR ProteinP43088 (Uniprot-TrEMBL)
Pentadecanoic acid MetaboliteCHEBI:42504 (ChEBI)
Phospho-Ribosomal protein S6 kinaseREACT_12696 (Reactome)
Protein Kinase C, alpha type DAGComplexREACT_18539 (Reactome)
QRFPProteinP83859 (Uniprot-TrEMBL)
QRFPR ProteinQ96P65 (Uniprot-TrEMBL)
RAF/MAP kinase cascadePathwayWP2735 (WikiPathways) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
RGS proteins active for G alpha REACT_24580 (Reactome)
RGZ MetaboliteCHEBI:50122 (ChEBI)
Ribosomal protein S6 kinaseREACT_13229 (Reactome)
SAA1ProteinP0DJI8 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
Substance P peptide ProteinP20366 (Uniprot-TrEMBL)
TAC3ProteinQ9UHF0 (Uniprot-TrEMBL)
TACR1 ProteinP25103 (Uniprot-TrEMBL)
TACR2 ProteinP21452 (Uniprot-TrEMBL)
TACR3 ProteinP29371 (Uniprot-TrEMBL)
TBXA2RProteinP21731 (Uniprot-TrEMBL)
TRHProteinP20396 (Uniprot-TrEMBL)
TRHR ProteinP34981 (Uniprot-TrEMBL)
TRIO ProteinO75962 (Uniprot-TrEMBL)
TRIO family RhoGEFsProteinREACT_20038 (Reactome)
TXA2 MetaboliteCHEBI:15627 (ChEBI)
UDP MetaboliteCHEBI:17659 (ChEBI)
UTS2BProteinQ765I0 (Uniprot-TrEMBL)
UTS2ProteinO95399 (Uniprot-TrEMBL)
UTS2R ProteinQ9UKP6 (Uniprot-TrEMBL)
Valerate MetaboliteCHEBI:31011 (ChEBI)
XCL1 ProteinP47992 (Uniprot-TrEMBL)
XCL2 ProteinQ9UBD3 (Uniprot-TrEMBL)
XCR1 ProteinP46094 (Uniprot-TrEMBL)
p-6Y-EGFR ProteinP00533 (Uniprot-TrEMBL)
p-ERK1/2/5ProteinREACT_13301 (Reactome)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_12487 (Reactome)
ADPArrowREACT_12622 (Reactome)
ADRBK1REACT_19213 (Reactome)
ATPREACT_12487 (Reactome)
ATPREACT_12622 (Reactome)
CCKBRREACT_121113 (Reactome)
CREB1REACT_12622 (Reactome)
DAGArrowREACT_960 (Reactome)
DAGREACT_18303 (Reactome)
EGFRREACT_121381 (Reactome)
G-protein alpha ArrowREACT_22263 (Reactome)
G-protein alpha REACT_19172 (Reactome)
G-protein alpha REACT_19186 (Reactome)
G-protein alpha REACT_19213 (Reactome)
G-protein alpha REACT_19270 (Reactome)
G-protein alpha REACT_19301 (Reactome)
G-protein alpha REACT_19325 (Reactome)
G-protein alpha REACT_22425 (Reactome)
G-protein beta-gamma complexArrowREACT_22263 (Reactome)
G-protein beta-gamma complexREACT_22425 (Reactome)
GASTREACT_121113 (Reactome)
GDPArrowREACT_121377 (Reactome)
GDPArrowREACT_15291 (Reactome)
GPCRs that activate Gq/11ArrowREACT_22263 (Reactome)
GRB2

SOS1 HB-EGF

p-6Y-EGFR		REACT_121377 (Reactome)
GRB2 SOS1REACT_121250 (Reactome)
GRK5REACT_19325 (Reactome)
GTPREACT_121377 (Reactome)
GTPREACT_15291 (Reactome)
HB-EGF p-6Y-EGFR dimerREACT_121250 (Reactome)
HBEGFArrowREACT_121027 (Reactome)
HBEGFREACT_121381 (Reactome)
Heterotrimeric G-protein Gq/11 REACT_22436 (Reactome)
IArrowREACT_960 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		ArrowREACT_15291 (Reactome)
Ligand

GPCR complexes that activate Gq/11

Heterotrimeric G-protein Gq 		REACT_15291 (Reactome)
Ligand GPCR complexes that activate Gq/11REACT_22436 (Reactome)
Ligands of GPCRs that activate Gq/11ArrowREACT_22263 (Reactome)
MMP3REACT_121027 (Reactome)
PI3K alphaREACT_19172 (Reactome)
PLC beta G alpha REACT_960 (Reactome)
PLC-betaREACT_19270 (Reactome)
PRKCAREACT_18303 (Reactome)
Phospho-Ribosomal protein S6 kinaseArrowREACT_12487 (Reactome)
Phospho-Ribosomal protein S6 kinaseREACT_12622 (Reactome)
Protein Kinase C, alpha type DAGREACT_120731 (Reactome)
REACT_120731 (Reactome) Gastrin activated PKC pathway leads to the induction of matrix metalloproteinase 3 (MMP3) synthesis (Reuben et al. 2002). The cleavage and autocatalysis steps to obtain the fully activated form of MMP3 have been omitted here.
REACT_121027 (Reactome) Gastrin can induce cleavage of pro-HBEGF via MMP3, releasing mature HBEGF. This event is based on evidence from mouse experiments (Suzuki et al. 1997).
REACT_121113 (Reactome) Gastrin receptors (gastric cholecystokinin B receptor, CCK-BR) mediate acid secretion from parietal cells, release of histamine from enterochromaffin-like (ECL) cells and contraction of smooth muscle (Ito et al. 1993).The hormone gastrin is the central regulator of gastric acid secretion and in addition, plays a prominent role in regulation of growth and differentiation of gastric and colonic mucosa.
REACT_121250 (Reactome) Cytoplasmic target proteins containing the SH2 domain can bind to activated EGFR. One such protein, growth factor receptor-bound protein 2 (GRB2), can bind activated EGFR with its SH2 domain whilst in complex with SOS through its SH3 domain. GRB2 can bind at either Y1068 and/or Y1086 autophosphorylation sites on the receptor (Batzer et al. 1994, Okutani et al. 1994).
REACT_121377 (Reactome) SOS1 is the guanine nucleotide exchange factor (GEF) for RAS. SOS1 activates RAS nucleotide exchange from the inactive form (bound to GDP) to an active form (bound to GTP) (Chardin et al. 1993).
REACT_121381 (Reactome) The heparin-binding EGF growth factor (HBEGF) is a member of the EGF family of growth factors that binds to and activates the EGF receptor EGFR/ErbB1 and ErbB4 (not shown here) (Higashiyama et al. 1991, Elenius et al. 1997). The details which describe receptor dimerisation on ligand binding and autophosphorylation from experiments in mice have been omitted here.
REACT_12487 (Reactome) The p90 ribosomal S6 kinases (RSK1-4) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. RSK family members are unusual among serine/threonine kinases in that they contain two distinct kinase domains, both of which are catalytically functional . The C-terminal kinase domain is believed to be involved in autophosphorylation, a critical step in RSK activation, whereas the N-terminal kinase domain, which is homologous to members of the AGC superfamily of kinases, is responsible for the phosphorylation of all known exogenous substrates of RSK.
RSKs can be activated by the ERKs (ERK1, 2, 5) in the cytoplasm as well as in the nucleus, they both have cytoplasmic and nuclear substrates, and they are able to move from nucleus to cytoplasm. Efficient RSK activation by ERKs requires its interaction through a docking site located near the RSK C terminus. The mechanism of RSK activation has been studied mainly with regard to ERK1 and ERK2. RSK activation leads to the phosphorylation of four essential residues Ser239, Ser381, Ser398, and Thr590, and two additional sites, Thr377 and Ser749 (the amino acid numbering refers to RSK1). ERK is thought to play at least two roles in RSK1 activation. First, activated ERK phosphorylates RSK1 on Thr590, and possibly on Thr377 and Ser381, and second, ERK brings RSK1 into close proximity to membrane-associated kinases that may phosphorylate RSK1 on Ser381 and Ser398.
Moreover, RSKs and ERK1/2 form a complex that transiently dissociates upon growth factor signalling. Complex dissociation requires phosphorylation of RSK1 serine 749, a growth factor regulated phosphorylation site located near the ERK docking site. Serine 749 is phosphorylated by the N-terminal kinase domain of RSK1 itself. ERK1/2 docking to RSK2 and RSK3 is also regulated in a similar way. The length of RSK activation following growth factor stimulation depends on the duration of the RSK/ERK complex, which, in turn, differs among the different RSK isoforms. RSK1 and RSK2 readily dissociate from ERK1/2 following growth factor stimulation stimulation, but RSK3 remains associated with active ERK1/2 longer, and also remains active longer than RSK1 and RSK2.

REACT_12622 (Reactome) CREB is phosphorylated at Serine 133 by RSK1/2/3.
REACT_15291 (Reactome) G alpha q protein (or Gq/11) consists of four family members (G-alpha 11, -alpha 14, -alpha 15 and -alpha q). It activates phospholipase C (PLC) (Dowal L et al, 2006). PLC hydrolyzes phosphatidylinositol (PIP2) to diacyl glycerol (DAG) and inositol triphosphate (IP3). DAG acts as a second messenger that activates protein kinase C (PKC) and IP3 can bind to IP3 receptors, particular calcium channels in the endoplasmic reticulum (ER). Calcium flow causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity.
REACT_18303 (Reactome) Diacylglycerol, produced by PLC beta-mediated PIP2 hydrolysis in G alpha (q) signalling, remains in the plasma membrane and binds Protein Kinase C alpha (PKC-alpha), causing PKC-alpha to translocate from the cytosol to the plasma membrane. PKC-alpha is thereby activated and phosphorylates target proteins.
REACT_19172 (Reactome) Phospholipase C activation is the classical signalling route for G alpha (q) but an additional mechanism is an inhibitory interaction between G alpha (q) and phosphatidylinositol 3-kinase alpha (PI3K alpha). There are several PI3K subtypes but only the p85 alpha/p110 alpha subtype (PI3K alpha) is a G alpha (q) effector (PMID: 18515384). Activated G alpha (q) inhibits PI3K alpha directly, in a GTP-dependent manner. G alpha(q) binding of PI3K competes with Ras, a PI3K activator (PMID: 16268778).
REACT_19186 (Reactome) When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region.
REACT_19213 (Reactome) GRK2 can inhibit GPCR signaling via phosphorylation-independent sequestration of Gq/11/14 subunits utilising its RGS homology (RH) domain. GRK2 may be an effector of activated Gq, initiating signalling cascades other than the classical PLC beta signalling associated with Gq.
REACT_19270 (Reactome) The active form of G protein alpha subunit q (Gq-alpha) was found to activate phospholipase C beta-1 (PLC-beta1), in investigations using bovine membranes. Subsequently, all 4 human isoforms have been shown to be activated by Gq, though activation of PLCbeta-4 is limited. In recombinant assays, several activated rat G alpha q family members were found to stimulate human PLC-beta isoforms with the same rank order of decreasing potency. PLC-beta1 stimulation was slightly more than for PLC-beta3; PLC-beta3 stimulation was 10-fold greater than for beta-2. PLC-beta2 is expressed specifically in hematopoietic cells. PLC-beta acts directly on Gq to accelerate hydrolysis of bound GTP, thus PLC-betas are GTPase activating proteins (GAPs). The crystal structure of the C-terminal region from Turkey PLC-beta, revealed a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The extent of the dimer interface and gel exclusion chromatography data suggest that PLC-betas are functionally dimeric.
REACT_19301 (Reactome) The Trio family of RhoA guanine nucleotide exchange factors (RhoGEFs) are directly activated by G alpha (q), possibly within a Gq:Trio:RhoA signalling complex, thereby linking Gq to RhoA-mediated processes such as cell migration, proliferation, and contraction. Like most other RhoGEFs, they have a tandem motif consisting of a Dbl homology (DH) and a pleckstrin homology (PH) domain. Trio and Duet have a number of other domains including an immunoglobin domains that may be involved in interacting with Rho, but the considerably smaller GEFT (p63RhoGEF) does not have any identifiable additional domains yet appears to be sufficient to mediate the activation of RhoA by G alpha (q). The structure represented by GEFT is proposed to represent the core of an ancient signal transduction pathway.
REACT_19325 (Reactome) GRKs are serine/threonine kinases that phosphorylate GPCRs leading to receptor desensitization. GRK5 appears to be the predominant regulator of PAR1 desensitization in endothelial cells.
REACT_22263 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (q) and the beta:gamma dimer then participate in separate signaling cascades. Although G protein dissociation has been contested (e.g. Bassi et al. 1996), recent in vivo experiments have demonstrated that dissociation does occur, though possibly not to completion (Lambert 2008).
REACT_22425 (Reactome) The classical model of G-protein signaling suggests that the G-protein dissociates upon GPCR activation. The active G alpha (q) subunit then participates in signaling, until its intrinsic GTPase activity degrades the bound GTP to GDP. The inactive G alpha (q):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates.
REACT_22436 (Reactome) Numerous functionally unrelated GPCRs couple with the Gq G-protein subtype.
REACT_960 (Reactome) Phospholipase C (PLC) isozymes are a group of related proteins that cleave the polar head group from inositol phospholipids, typically in response to signals from cell surface receptors. They hydrolyze the highly phosphorylated lipid phosphatidylinositol 4,5-bisphosphate (PIP2) generating two products: inositol 1,4,5-trisphosphate (IP3), a universal calcium-mobilizing second messenger, and diacylglycerol (DAG), an activator of protein kinase C. PLC-beta isoforms are regulated by heterotrimeric GTP-binding proteins. PLC-beta 1 and 3 are widely expressed, with the highest concentrations found in (differing) specific regions of the brain. PLC-beta 2 is expressed at highest levels in cells of hematopoeitic origin; it is involved in leukocyte signaling and host defense. PLC-beta 4 is highly concentrated in cerebellar Purkinje and granule cells, the median geniculate body, whose axons terminate in the auditory cortex, and the lateral geniculate nucleus, where most retinal axons terminate in a visuotopic representation of each half of the visual field.
RGS proteins active for G alpha ArrowREACT_19186 (Reactome)
Ribosomal protein S6 kinaseREACT_12487 (Reactome)
TRIO family RhoGEFsREACT_19301 (Reactome)
p-ERK1/2/5REACT_12487 (Reactome)
p-S133-CREB1ArrowREACT_12622 (Reactome)
p21 RAS GDPREACT_121377 (Reactome)
p21 RAS GTPArrowREACT_121377 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2664"
Personal tools