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

From WikiPathways

Revision as of 13:46, 8 May 2014 by Anwesha (Talk | contribs)
Jump to: navigation, search
9, 28, 3713, 2314, 345, 22, 29, 32, 35393627218, 2431519, 412916101716, 387, 26418Prokineticin receptors P2RY11 ATP G-protein beta-gamma complex Carboxylate ligands of FFAR3 QRFP receptorQRFP OxytocinOxytocin receptor Urotensin 2, 2B Chemokine XC receptor 1 XC1 ligands Neuropeptide FF receptorNeuropeptide FF pH sensing receptors CHRM1, 3, 5 pH sensing receptors GRB2SOS1 G-protein alpha G-protein alpha pH sensing receptorsH+ Neuromedin-U receptors Neurotensin receptor GnRH receptorGNRH ligands P2RY5LPA Acyl Ghrelin G-protein beta-gamma complex nucleoplasmp21 RAS G-protein beta-gamma complex Neuromedin-UNeuromedin receptors EP1 receptorPGE2 HRH1Histamine G-protein beta-gamma complex Alpha-1 adrenoceptor GlucagonGCGR P2RY2ATP TRH Bombesin-like peptide NPSNPSR Cysteinyl leukotriene receptors G-protein alpha Cysteinyl leukotriene receptorsCysteinyl leukotrienes Melanospinphoton LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq G-protein alpha LigandGPCR complexes that activate Gq/11 LPA-binding EDG receptors Neurotensin receptor G-protein alpha Heterotrimeric G-protein Gq/11 Bradykinin receptor Endothelin receptor G-protein alpha Substance P receptorSubstance P peptide Neuromedin-U receptors CASRCalcium Urotensin 2, 2B Carboxylate ligands of FFAR3 5-HT2 receptorSerotonin MetastinKiSS1R GPRC6A receptorGPRC6A ligands Group I Metabotropic glutamate receptors Orexin 2 receptorOrexin B GPR17UDP Melanospinphoton TRHTRHR M1/M3/M5acetylcholine LTB4 receptorsLTB4 GPRC6A receptorGPRC6A ligands Cholecystokinin receptors GnRH receptor Prokineticin TP receptorThromboxane A2 Bradykinin receptorBradykinin TRH Orexin 1 receptorOrexin A Group I Metabotropic glutamate receptorsGlu GPRC6A ligands CHRM1, 3, 5 HB-EGFp-6Y-EGFR dimer Proteinase-activated receptors G-protein alpha P2RY6UDP Motilin receptorMotilin LTB4 receptors G-protein alpha MCHMelanin-concentrating hormone receptors Ligands of FFAR1 Alpha-1 adrenoceptor GPR17UDP FPRL1 ligands EndothelinEndothelin receptor P2RY1ADP cytosolCatecholamine LPA-binding EDG receptors Alpha-1 adrenoceptorCatecholamine Cysteinyl leukotrienes GnRH receptorGNRH ligands LTB4 receptorsLTB4 GastrinCCKBR FPRL1FPRL1 ligands Substance P receptorSubstance P peptide pH sensing receptorsH+ Endothelin receptor Basic L-amino acids UTS2RUrotensin 2, 2B EndothelinEndothelin receptor Cholecystokinin receptors GnRH receptor Protein Kinase C, alpha type DAG Vasopressin receptor type 1AVP LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq UTS2RUrotensin 2, 2B Prokineticin MCHMelanin-concentrating hormone receptors FFAR1fatty acid G-protein alpha Substance K receptorNeurokinin A peptide Neuromedin-SNeuromedin-U receptor 2 LPA-binding EDG receptors LPA FPRL1FPRL1 ligands Melanin-concentrating hormone receptors MetastinKiSS1R Orexin 1 receptorOrexin A ThrombinProteinase-activated receptors Type 1 angiotensin II receptorAngiotensin II G-protein alpha G-protein alpha Neuromedin-UNeuromedin receptors FP receptorPGF2-alpha QRFP receptorQRFP PLC betaG alpha GPRC6A ligands Ligands of FFAR1 Melanin-concentrating hormone receptors Endothelin XC1 ligands Vasopressin receptor type 1 Orexin 2 receptorOrexin B HB-EGFp-6Y-EGFR dimer Vasopressin receptor type 1AVP GRB2SOS1 Carboxylate ligands of FFAR2 G-protein alpha Neuromedin-SNeuromedin-U receptor 2 Motilin receptorMotilin CCKCholecystokinin receptors Neuromedin K receptorNeurokinin B peptide OxytocinOxytocin receptor P2RY5LPA G-protein alpha TRHTRHR p21 RASGDP Neuropeptide FF receptorNeuropeptide FF G-protein alpha GNRH ligands G-protein alpha Substance K receptorNeurokinin A peptide 5-HT2 receptor Bradykinin receptorBradykinin FFAR2Carboxylate ligands EP1 receptorPGE2 P2RY11 ATP G-protein alpha Chemokine XC receptor 1 XC1 ligands Prokineticin receptorsprokineticin P2RY9LPA G-protein alpha FFAR3Carboxylate ligands ThrombinProteinase-activated receptors PAF receptorPAF p21 RAS FFAR1fatty acid XC1 ligands TRIO family RhoGEFs PLC-beta PI3K alpha G-protein alpha P2RY2ATP Bradykinin receptor Group I Metabotropic glutamate receptorsGlu Endothelin G-protein alpha CASRCalcium TP receptorThromboxane A2 Neuromedin K receptorNeurokinin B peptide Heterotrimeric G-protein Gq/11 P2RY10LPA LigandGPCR complexes that activate Gq/11 HB-EGFp-6Y-EGFR Bombesin-like receptorbombesin-like peptide Proteinase-activated receptors Acyl ghrelinGHSR FPRL1 ligands PI3K alpha Alpha-1 adrenoceptorCatecholamine G-protein alpha Neuropeptide FF receptor Carboxylate ligands of FFAR2 G-protein alpha G-protein alpha Prokineticin receptors FFAR3Carboxylate ligands GRB2SOS1HB-EGFp-6Y-EGFR p21 RASGTP Cysteinyl leukotrienes Heterotrimeric G-protein Gq Cysteinyl leukotriene receptors HB-EGFp-6Y-EGFR HRH1Histamine CCKCholecystokinin receptors 5-HT2 receptorSerotonin LPA-binding EDG receptors LPA NeurotensinNeurotensin receptor Cysteinyl leukotriene receptorsCysteinyl leukotrienes G-protein alpha G-protein alpha FP receptorPGF2-alpha Group I Metabotropic glutamate receptors Vasopressin receptor type 1 Basic L-amino acids Bombesin-like peptide P2RY10LPA GastrinCCKBR FFAR2Carboxylate ligands P2RY6UDP Neuropeptide FF receptor NPSNPSR P2RY1ADP Acyl ghrelinGHSR NeurotensinNeurotensin receptor Activated thrombin M1/M3/M5acetylcholine LTB4 receptors Prokineticin receptorsprokineticin Acyl Ghrelin GlucagonGCGR P2RY9LPA Bombesin-like receptorbombesin-like peptide GNRH ligands Type 1 angiotensin II receptorAngiotensin II 5-HT2 receptor Activated thrombin Catecholamine PAF receptorPAF GastrinCCKBR PLC-betaGNA14 HTR2B LTE4 PIK3CA P2RY1 P2RY10 DecS-GHRL-15HT GNA14 G-protein alpha ATPGNA14 NTSR2 ATP TBXA2RLPAR3 GRPGastrinCCKBRP2RY10 NMUR2 FPR2 BDKRB1 TRIO LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq O-octanoyl-L-serine-GHRL-1PTGER1 LPAR4 LTB4R2 MCHR2 GPR68 Hist MMP3OXTR O-octanoyl-L-serine-GHRL-1GPRC6A P2RY11 GDP QRFPGNAQ PLCB1 Glu GRM1 ADPGRM5 SAA1IEDNRA LTB4R2 CCKAR ADRA1A GNA15 CHRM3 HBEGFTRHGASTGRM5 ADRBK1PROK1 GTP BDKRB1 PROK2 PGF2a GPR132 GNA15 RGZ PLCB2 LTD4 TRHR AVPR1B ADR GRK5 GNA15 XCL1 Pentadecanoic acid MLNR TRHCREB1GNA15 HTR2CPTGER1 HCRTR1 AVPBUT Hist TRHLPAR1 PLC betaG alpha OPN4 CHRM1 F2RTACR3 ANXA1 H+ p-6Y-EGFR Neurokinin A peptide PALM NPFFL-Lys APPGNA15 GNA11 LPAR6 LTE4 GDP GNA14 PRKCA CYSLTR2 EDNRB TXA2 PALM ARHGEF25 GRB2SOS1HB-EGFp-6Y-EGFREDN1ADRA1A MT-RNR2HCRTR2 G-protein alpha Glucagon GRB2SOS1OXTOXTR TRHP2RY1 GDPSAA1G-protein alpha FFAR3 G-protein beta-gamma complexNRAS NMBAVPR1A GCGR HCOOH LTC4 EtCOO- or C2H5COO- GRK5GNAQ FFAR1 GNA15 APPTRHR ADRBK1PGE2 TRHNMUR2 CYSLTR1 PROKR2 GNA14 HCRTHTR2CMCHR2 DecS-GHRL-1LTB4R ATP HBEGFHCRTGNA11 GPR65 UTS2R Bradykinin TAC3RGZ TAC3HRASNTSR2 GNRH2BDKRB2 GNA11 thrombin heavy chain AVPR1A TRHGTPAGTR1 LPAR1 GPR17 p-S133-CREB1UTS2R CCKBR GNA11 AVPRibosomal protein S6 kinaseF2RL1NMSp-6Y-EGFR TRHHCRTR2 FFAR3 AGTBradykinin GDP SOS1 L-Arg G-protein alpha Effects of PIP2 hydrolysisCHRM5 UTS2CASR LPAR4 GTPTACR1 CYSLTR1 p21 RASGTPPAF LTC4 CH3COO- L-Orn KALRN NPSGlucagon TRHXCR1 F2RL3HBEGFFFAR2 O-octanoyl-L-serine-GHRL-1LPAR2 FPR2 GTP NPFFR1 CCKAR ANXA1 F2RL3GNAQ UTS2CHRM5 Substance P peptide LPAR3 CH3COO- GASTGDP FFAR1 DAGValerate HRH1 DecS-GHRL-1TRIO family RhoGEFsDDCX EDN3LPAR5 QRFPR GPR17 XCL1 OLEA GNA11 UDP HTR2A GPR4 EDN1HCOOH QRFPAGTNPSR1 ADPGNA14 L-Orn BUT GPRC6A NMUR1 PGE2 NMUR1 G-protein alpha GDPNTSOXTL-Lys Phospho-Ribosomal protein S6 kinaseMCHR1 LTB4 NTSCCKBR PAF PTAFR GNRHR NPSp-ERK1/2/5CCKBRG-protein alpha PROKR1 GNA15 RAF/MAP kinase cascadeADP NPFFR2 CYSLTR2 UDP ADRA1B PGF2a DecS-GHRL-1NPFFR1 LPAR6 p21 RASGDPF2RL2Glu CHRM3 ADRA1D XCR1 AcCho QRFPR DDCX HCRTLPA PMCHCa2+ KISS1R PROK2 ADRA1B PI3K alphaGASTHRH1 F2RL2GNA14 GTP SOS1 GTP TACR3 NPSR1 Neurokinin A peptide thrombin light chain HXA GNAQ PTGFR PMCHPRKCAGRB2-1 NPFFEtCOO- or C2H5COO- ADRA1D GNA11 TXA2 KISS1HBEGFLigands of GPCRs that activate Gq/11GNA15 AVPR1B NAd GPR132 GPCRs that activate Gq/11AcCho GNRH1KISS1GNRHR2P2RY6 GNA15 PROK1 TRHOLEA GNAQ CASR HBEGFGNA14 TACR2 ATPLigandGPCR complexes that activate Gq/11HTR2B NTSR1 CCK NMBEGFRTACR2 NMUGASTNTSR1 MLNGNAQ 5HT AGTR1 EDNRA GNAQ GNRH2GNA14 O-octanoyl-L-serine-GHRL-1Substance P peptide CCKBR HBEGFPIUTS2BPLCB4 P2RY11 GRM1 NRAS Ca2+ TACR1 LPAR5 GNAQ GNA11 GRB2-1 PROKR2 TRHEDNRB GTP GNA11 GTP PTAFR KISS1R GTP NMUGNA15 RGS proteins active for G alpha LXA4 MLNR thrombin light chain GPR68 CCL23-2 OPN4 GNRHR2GPR65 GNAQ TBXA2RP2RY6 HCRTR1 P2RY2 LTB4R CHRM1 GRPGPR4 EDN2PTGFR GHSR FFAR2 KRASL-Arg GNRH1MCHR1 Pentadecanoic acid Valerate LTB4 ADR GNA14 NAd LTD4 XCL2 H+ P2RY2 TRHMLNG-protein alpha HRASCCK GHSR CCL23-2 LPA LPAR2 LXA4 TRHGTP GNA11 GCGR HCRTPIK3CA BDKRB2 NPFFR2 thrombin heavy chain GNRHR Protein Kinase C, alpha type DAGEDN2PLCB3ADP LigandGPCR complexes that activate Gq/11Heterotrimeric G-protein Gq UTS2BNMSGNAQ HXA DAG F2RL1XCL2 F2RHB-EGFp-6Y-EGFR dimerGNA11 Heterotrimeric G-protein Gq/11 MT-RNR2HTR2A EDN3KRASPROKR1 25, 4030, 312, 12, 3325, 4025, 4011, 2025, 40


Description

No description

Comments

Wikipathways-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)
Personal tools