Gastrin-CREB signaling via PKC and MAPK (Homo sapiens)
From 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
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| 5HT [extracellular region] | Metabolite | CHEBI:28790 (ChEBI)  | |
| ADP [extracellular region] | Metabolite | CHEBI:16761 (ChEBI) | |
| ADP | Metabolite | CHEBI:16761 (ChEBI) | |
| ADR [extracellular region] | Metabolite | CHEBI:28918 (ChEBI) | |
| ADRA1A [plasma membrane] | Protein | P35348 (Uniprot-TrEMBL) | |
| ADRA1B [plasma membrane] | Protein | P35368 (Uniprot-TrEMBL) | |
| ADRA1D [plasma membrane] | Protein | P25100 (Uniprot-TrEMBL) | |
| ADRBK1(2-689) [plasma membrane] | Protein | P25098 (Uniprot-TrEMBL) | |
| ADRBK1(2-689) | Protein | P25098 (Uniprot-TrEMBL) | |
| AGT(34-41)
[extracellular region] | Protein | P01019 (Uniprot-TrEMBL) | |
| AGTR1 [plasma membrane] | Protein | P30556 (Uniprot-TrEMBL) | |
| ANXA1 [extracellular region] | Protein | P04083 (Uniprot-TrEMBL) | |
| APP(672-713)
[extracellular region] | Protein | P05067 (Uniprot-TrEMBL) | |
| ARHGEF25 [cytosol] | Protein | Q86VW2 (Uniprot-TrEMBL) | |
| ATP [extracellular region] | Metabolite | CHEBI:15422 (ChEBI) | |
| ATP | Metabolite | CHEBI:15422 (ChEBI) | |
| AVP(20-28)
[extracellular region] | Protein | P01185 (Uniprot-TrEMBL) | |
| AVPR1A [plasma membrane] | Protein | P37288 (Uniprot-TrEMBL) | |
| AVPR1B [plasma membrane] | Protein | P47901 (Uniprot-TrEMBL) | |
| AcCho [extracellular region] | Metabolite | CHEBI:15355 (ChEBI) | |
| BDKRB1 [plasma membrane] | Protein | P46663 (Uniprot-TrEMBL) | |
| BDKRB2 [plasma membrane] | Protein | P30411 (Uniprot-TrEMBL) | |
| BUT [extracellular region] | Metabolite | CHEBI:30772 (ChEBI) | |
| Bradykinin
[extracellular region] | Protein | P01042 (Uniprot-TrEMBL) | |
| CASR [plasma membrane] | Protein | P41180 (Uniprot-TrEMBL) | |
| CCK [extracellular region] | Protein | P06307 (Uniprot-TrEMBL) | |
| CCKAR [plasma membrane] | Protein | P32238 (Uniprot-TrEMBL) | |
| CCKBR [plasma membrane] | Protein | P32239 (Uniprot-TrEMBL) | |
| CCKBR | Protein | P32239 (Uniprot-TrEMBL) | |
| CCL23-2
[extracellular region] | Protein | P55773-2 (Uniprot-TrEMBL) | |
| CH3COO-
[extracellular region] | Metabolite | CHEBI:15366 (ChEBI) | |
| CHRM1 [plasma membrane] | Protein | P11229 (Uniprot-TrEMBL) | |
| CHRM3 [plasma membrane] | Protein | P20309 (Uniprot-TrEMBL) | |
| CHRM5 [plasma membrane] | Protein | P08912 (Uniprot-TrEMBL) | |
| CREB1 | Protein | P16220 (Uniprot-TrEMBL) | |
| CYSLTR1 [plasma membrane] | Protein | Q9Y271 (Uniprot-TrEMBL) | |
| CYSLTR2 [plasma membrane] | Protein | Q9NS75 (Uniprot-TrEMBL) | |
| Ca2+ [extracellular region] | Metabolite | CHEBI:29108 (ChEBI) | |
| DAG [plasma membrane] | Metabolite | CHEBI:17815 (ChEBI) | |
| DAG | Metabolite | CHEBI:17815 (ChEBI) | |
| DDCX [plasma membrane] | Metabolite | CHEBI:30805 (ChEBI) | |
| DecS-GHRL-1(24-50)
[extracellular region] | Protein | Q9UBU3-1 (Uniprot-TrEMBL) | |
| DecS-GHRL-1(24-51)
[extracellular region] | Protein | Q9UBU3-1 (Uniprot-TrEMBL) | |
| EDN1(53-73)
[extracellular region] | Protein | P05305 (Uniprot-TrEMBL) | |
| EDN2(49-69)
[extracellular region] | Protein | P20800 (Uniprot-TrEMBL) | |
| EDN3(97-117)
[extracellular region] | Protein | P14138 (Uniprot-TrEMBL) | |
| EDNRA [plasma membrane] | Protein | P25101 (Uniprot-TrEMBL) | |
| EDNRB [plasma membrane] | Protein | P24530 (Uniprot-TrEMBL) | |
| EGFR | Protein | P00533 (Uniprot-TrEMBL) | |
| Effects of PIP2 hydrolysis | Pathway | WP1809 (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-
[extracellular region] | Metabolite | CHEBI:30768 (ChEBI) | |
| F2R(27-425) [plasma membrane] | Protein | P25116 (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) [plasma membrane] | Protein | P55085 (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) [plasma membrane] | Protein | O00254 (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) [plasma membrane] | Protein | Q96RI0 (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 [plasma membrane] | Protein | O14842 (Uniprot-TrEMBL) | |
| FFAR2 [plasma membrane] | Protein | O15552 (Uniprot-TrEMBL) | |
| FFAR3 [plasma membrane] | Protein | O14843 (Uniprot-TrEMBL) | |
| FPR2 [plasma membrane] | Protein | P25090 (Uniprot-TrEMBL) | |
| G-protein alpha (q):GRK2 | Complex | REACT_19587 (Reactome) | |
| G-protein alpha (q):GRK5 | Complex | REACT_19592 (Reactome) | |
| G-protein alpha (q/11): GTP | Complex | REACT_5863 (Reactome) | |
| G-protein alpha (q/11):GDP | Complex | REACT_3769 (Reactome) | |
| G-protein alpha (q/11):PI3K alpha | Complex | REACT_20202 (Reactome) | |
| G-protein alpha
(q/11):Trio family RhoGEFs | Complex | REACT_19870 (Reactome) | |
| G-protein alpha (q/11) | Protein | REACT_18229 (Reactome) | |
| G-protein beta-gamma complex | Complex | REACT_15674 (Reactome) | |
| GAST(76-92)
[extracellular region] | Protein | P01350 (Uniprot-TrEMBL) | |
| GAST(76-92) | Protein | P01350 (Uniprot-TrEMBL) | |
| GCGR [plasma membrane] | Protein | P47871 (Uniprot-TrEMBL) | |
| GDP [cytosol] | Metabolite | CHEBI:17552 (ChEBI) | |
| GDP [plasma membrane] | Metabolite | CHEBI:17552 (ChEBI) | |
| GDP | Metabolite | CHEBI:17552 (ChEBI) | |
| GHSR [plasma membrane] | Protein | Q92847 (Uniprot-TrEMBL) | |
| GNA11 [plasma membrane] | Protein | P29992 (Uniprot-TrEMBL) | |
| GNA14 [plasma membrane] | Protein | O95837 (Uniprot-TrEMBL) | |
| GNA15 [plasma membrane] | Protein | P30679 (Uniprot-TrEMBL) | |
| GNAQ [plasma membrane] | Protein | P50148 (Uniprot-TrEMBL) | |
| GNRH1(24-33)
[extracellular region] | Protein | P01148 (Uniprot-TrEMBL) | |
| GNRH2(24-33)
[extracellular region] | Protein | O43555 (Uniprot-TrEMBL) | |
| GNRHR [plasma membrane] | Protein | P30968 (Uniprot-TrEMBL) | |
| GNRHR2(1-178) [plasma membrane] | Protein | Q96P88 (Uniprot-TrEMBL) | |
| GPCRs that activate Gq/11 | Protein | REACT_22567 (Reactome) | |
| GPR132 [plasma membrane] | Protein | Q9UNW8 (Uniprot-TrEMBL) | |
| GPR17 [plasma membrane] | Protein | Q13304 (Uniprot-TrEMBL) | |
| GPR4 [plasma membrane] | Protein | P46093 (Uniprot-TrEMBL) | |
| GPR65 [plasma membrane] | Protein | Q8IYL9 (Uniprot-TrEMBL) | |
| GPR68 [plasma membrane] | Protein | Q15743 (Uniprot-TrEMBL) | |
| GPRC6A [plasma membrane] | Protein | Q5T6X5 (Uniprot-TrEMBL) | |
| GRB2-1 [cytosol] | Protein | P62993-1 (Uniprot-TrEMBL) | |
| GRB2:SOS1:HB-EGF:p-6Y-EGFR | Complex | REACT_124650 (Reactome) | |
| GRB2:SOS1 | Complex | REACT_4435 (Reactome) | |
| GRK5 [cytosol] | Protein | P34947 (Uniprot-TrEMBL) | |
| GRK5 | Protein | P34947 (Uniprot-TrEMBL) | |
| GRM1 [plasma membrane] | Protein | Q13255 (Uniprot-TrEMBL) | |
| GRM5 [plasma membrane] | Protein | P41594 (Uniprot-TrEMBL) | |
| GRP(24-50)
[extracellular region] | Protein | P07492 (Uniprot-TrEMBL) | |
| GTP [cytosol] | Metabolite | CHEBI:15996 (ChEBI) | |
| GTP [plasma membrane] | Metabolite | CHEBI:15996 (ChEBI) | |
| GTP | Metabolite | CHEBI:15996 (ChEBI) | |
| Gastrin:CCKBR | Complex | REACT_24587 (Reactome) | |
| Glu [extracellular region] | Metabolite | CHEBI:16015 (ChEBI) | |
| Glucagon
[extracellular region] | Protein | P01275 (Uniprot-TrEMBL) | |
| H+ [extracellular region] | Metabolite | CHEBI:15378 (ChEBI) | |
| HB-EGF:p-6Y-EGFR dimer | Complex | REACT_123414 (Reactome) | |
| HBEGF(149-208) | Protein | Q99075 (Uniprot-TrEMBL) | |
| HBEGF(20-208) | Protein | Q99075 (Uniprot-TrEMBL) | |
| HBEGF(20-62) | Protein | Q99075 (Uniprot-TrEMBL) | |
| HBEGF(63-148)
[extracellular region] | Protein | Q99075 (Uniprot-TrEMBL) | |
| HBEGF(63-148) | Protein | Q99075 (Uniprot-TrEMBL) | |
| HCOOH [extracellular region] | Metabolite | CHEBI:30751 (ChEBI) | |
| HCRT(34-66)
[extracellular region] | Protein | O43612 (Uniprot-TrEMBL) | |
| HCRT(70-97)
[extracellular region] | Protein | O43612 (Uniprot-TrEMBL) | |
| HCRTR1 [plasma membrane] | Protein | O43613 (Uniprot-TrEMBL) | |
| HCRTR2 [plasma membrane] | Protein | O43614 (Uniprot-TrEMBL) | |
| HRAS(1-186) [plasma membrane] | Protein | P01112 (Uniprot-TrEMBL) | |
| HRH1 [plasma membrane] | Protein | P35367 (Uniprot-TrEMBL) | |
| HTR2A [plasma membrane] | Protein | P28223 (Uniprot-TrEMBL) | |
| HTR2B [plasma membrane] | Protein | P41595 (Uniprot-TrEMBL) | |
| HTR2C(1-458) [plasma membrane] | Protein | P28335 (Uniprot-TrEMBL) | |
| HXA [extracellular region] | Metabolite | CHEBI:17120 (ChEBI) | |
| Heterotrimeric
G-protein Gq/11 (inactive) | Complex | REACT_5130 (Reactome) | |
| Hist [extracellular region] | Metabolite | CHEBI:18295 (ChEBI) | |
| I(1,4,5)P3 | Metabolite | CHEBI:16595 (ChEBI) | |
| KALRN [cytosol] | Protein | O60229 (Uniprot-TrEMBL) | |
| KISS1(68-121)
[extracellular region] | Protein | Q15726 (Uniprot-TrEMBL) | |
| KISS1R [plasma membrane] | Protein | Q969F8 (Uniprot-TrEMBL) | |
| KRAS(1-186) [plasma membrane] | Protein | P01116 (Uniprot-TrEMBL) | |
| L-Arg [extracellular region] | Metabolite | CHEBI:16467 (ChEBI) | |
| L-Lys [extracellular region] | Metabolite | CHEBI:18019 (ChEBI) | |
| L-Orn [extracellular region] | Metabolite | CHEBI:15729 (ChEBI) | |
| LPA [extracellular region] | Metabolite | CHEBI:52288 (ChEBI) | |
| LPAR1 [plasma membrane] | Protein | Q92633 (Uniprot-TrEMBL) | |
| LPAR2 [plasma membrane] | Protein | Q9HBW0 (Uniprot-TrEMBL) | |
| LPAR3 [plasma membrane] | Protein | Q9UBY5 (Uniprot-TrEMBL) | |
| LPAR4 [plasma membrane] | Protein | Q99677 (Uniprot-TrEMBL) | |
| LPAR5 [plasma membrane] | Protein | Q9H1C0 (Uniprot-TrEMBL) | |
| LPAR6 [plasma membrane] | Protein | P43657 (Uniprot-TrEMBL) | |
| LTB4 [extracellular region] | Metabolite | CHEBI:15647 (ChEBI) | |
| LTB4R [plasma membrane] | Protein | Q15722 (Uniprot-TrEMBL) | |
| LTB4R2 [plasma membrane] | Protein | Q9NPC1 (Uniprot-TrEMBL) | |
| LTC4 [extracellular region] | Metabolite | CHEBI:16978 (ChEBI) | |
| LTD4 [extracellular region] | Metabolite | CHEBI:28666 (ChEBI) | |
| LTE4 [extracellular region] | Metabolite | CHEBI:15650 (ChEBI) | |
| LXA4 [extracellular region] | Metabolite | CHEBI:6498 (ChEBI) | |
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (active) | Complex | REACT_22589 (Reactome) | |
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (inactive) | Complex | REACT_22865 (Reactome) | |
| Ligand:GPCR
complexes that activate Gq/11 | Complex | REACT_18247 (Reactome) | |
| Ligands of GPCRs that activate Gq/11 | Metabolite | REACT_23264 (Reactome) | |
| MCHR1 [plasma membrane] | Protein | Q99705 (Uniprot-TrEMBL) | |
| MCHR2 [plasma membrane] | Protein | Q969V1 (Uniprot-TrEMBL) | |
| MLN(26-47)
[extracellular region] | Protein | P12872 (Uniprot-TrEMBL) | |
| MLNR [plasma membrane] | Protein | O43193 (Uniprot-TrEMBL) | |
| MMP3 | Protein | P08254 (Uniprot-TrEMBL) | |
| MT-RNR2(1-714)
[extracellular region] | Protein | Q8IVG9 (Uniprot-TrEMBL) | |
| NAd [extracellular region] | Metabolite | CHEBI:18357 (ChEBI) | |
| NMB(47-56)
[extracellular region] | Protein | P08949 (Uniprot-TrEMBL) | |
| NMS(109-141)
[extracellular region] | Protein | Q5H8A3 (Uniprot-TrEMBL) | |
| NMU(142-166)
[extracellular region] | Protein | P48645 (Uniprot-TrEMBL) | |
| NMUR1 [plasma membrane] | Protein | Q9HB89 (Uniprot-TrEMBL) | |
| NMUR2 [plasma membrane] | Protein | Q9GZQ4 (Uniprot-TrEMBL) | |
| NPFF(69-76)
[extracellular region] | Protein | O15130 (Uniprot-TrEMBL) | |
| NPFFR1 [plasma membrane] | Protein | Q9GZQ6 (Uniprot-TrEMBL) | |
| NPFFR2 [plasma membrane] | Protein | Q9Y5X5 (Uniprot-TrEMBL) | |
| NPS(1-467)
[extracellular region] | Protein | P0C0P6 (Uniprot-TrEMBL) | |
| NPSR1 [plasma membrane] | Protein | Q6W5P4 (Uniprot-TrEMBL) | |
| NRAS [plasma membrane] | Protein | P01111 (Uniprot-TrEMBL) | |
| NTS(151-163)
[extracellular region] | Protein | P30990 (Uniprot-TrEMBL) | |
| NTSR1 [plasma membrane] | Protein | P30989 (Uniprot-TrEMBL) | |
| NTSR2 [plasma membrane] | Protein | O95665 (Uniprot-TrEMBL) | |
| Neurokinin A peptide
[extracellular region] | Protein | P20366 (Uniprot-TrEMBL) | |
| O-octanoyl-L-serine-GHRL-1(24-50)
[extracellular region] | Protein | Q9UBU3-1 (Uniprot-TrEMBL) | |
| O-octanoyl-L-serine-GHRL-1(24-51)
[extracellular region] | Protein | Q9UBU3-1 (Uniprot-TrEMBL) | |
| OLEA [plasma membrane] | Metabolite | CHEBI:16196 (ChEBI) | |
| OPN4 [plasma membrane] | Protein | Q9UHM6 (Uniprot-TrEMBL) | |
| OXT(20-28)
[extracellular region] | Protein | P01178 (Uniprot-TrEMBL) | |
| OXTR [plasma membrane] | Protein | P30559 (Uniprot-TrEMBL) | |
| P2RY1 [plasma membrane] | Protein | P47900 (Uniprot-TrEMBL) | |
| P2RY10 [plasma membrane] | Protein | O00398 (Uniprot-TrEMBL) | |
| P2RY11 [plasma membrane] | Protein | Q96G91 (Uniprot-TrEMBL) | |
| P2RY2 [plasma membrane] | Protein | P41231 (Uniprot-TrEMBL) | |
| P2RY6 [plasma membrane] | Protein | Q15077 (Uniprot-TrEMBL) | |
| PAF [extracellular region] | Metabolite | CHEBI:52450 (ChEBI) | |
| PALM [plasma membrane] | Metabolite | CHEBI:15756 (ChEBI) | |
| PGE2 [extracellular region] | Metabolite | CHEBI:15551 (ChEBI) | |
| PGF2a [extracellular region] | Metabolite | CHEBI:15553 (ChEBI) | |
| PI(4,5)P2 | Metabolite | CHEBI:18348 (ChEBI) | |
| PI3K alpha | Complex | REACT_12697 (Reactome) | |
| PIK3CA [cytosol] | Protein | P42336 (Uniprot-TrEMBL) | |
| PLC beta:G alpha (q/11) | Complex | REACT_17363 (Reactome) | |
| PLC-beta | Protein | REACT_15673 (Reactome) | |
| PLCB1 [cytosol] | Protein | Q9NQ66 (Uniprot-TrEMBL) | |
| PLCB2 [cytosol] | Protein | Q00722 (Uniprot-TrEMBL) | |
| PLCB3(2-1234) [cytosol] | Protein | Q01970 (Uniprot-TrEMBL) | |
| PLCB4 [cytosol] | Protein | Q15147 (Uniprot-TrEMBL) | |
| PMCH(147-165)
[extracellular region] | Protein | P20382 (Uniprot-TrEMBL) | |
| PRKCA [plasma membrane] | Protein | P17252 (Uniprot-TrEMBL) | |
| PRKCA | Protein | P17252 (Uniprot-TrEMBL) | |
| PROK1 [extracellular region] | Protein | P58294 (Uniprot-TrEMBL) | |
| PROK2 [extracellular region] | Protein | Q9HC23 (Uniprot-TrEMBL) | |
| PROKR1 [plasma membrane] | Protein | Q8TCW9 (Uniprot-TrEMBL) | |
| PROKR2 [plasma membrane] | Protein | Q8NFJ6 (Uniprot-TrEMBL) | |
| PTAFR [plasma membrane] | Protein | P25105 (Uniprot-TrEMBL) | |
| PTGER1 [plasma membrane] | Protein | P34995 (Uniprot-TrEMBL) | |
| PTGFR [plasma membrane] | Protein | P43088 (Uniprot-TrEMBL) | |
| Pentadecanoic acid [plasma membrane] | Metabolite | CHEBI:42504 (ChEBI) | |
| Phospho-Ribosomal protein S6 kinase | REACT_12696 (Reactome) | ||
| Protein Kinase C, alpha type: DAG | Complex | REACT_18539 (Reactome) | |
| QRFP(91-133)
[extracellular region] | Protein | P83859 (Uniprot-TrEMBL) | |
| QRFPR [plasma membrane] | Protein | Q96P65 (Uniprot-TrEMBL) | |
| RAF/MAP kinase cascade | Pathway | WP2735 (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 (q) | REACT_24580 (Reactome) | ||
| RGZ [plasma membrane] | Metabolite | CHEBI:50122 (ChEBI) | |
| Ribosomal protein S6 kinase | REACT_13229 (Reactome) | ||
| SAA1(19-122)
[extracellular region] | Protein | P0DJI8 (Uniprot-TrEMBL) | |
| SOS1 [cytosol] | Protein | Q07889 (Uniprot-TrEMBL) | |
| Substance P peptide
[extracellular region] | Protein | P20366 (Uniprot-TrEMBL) | |
| TAC3(81-90)
[extracellular region] | Protein | Q9UHF0 (Uniprot-TrEMBL) | |
| TACR1 [plasma membrane] | Protein | P25103 (Uniprot-TrEMBL) | |
| TACR2 [plasma membrane] | Protein | P21452 (Uniprot-TrEMBL) | |
| TACR3 [plasma membrane] | Protein | P29371 (Uniprot-TrEMBL) | |
| TBXA2R(1-369) [plasma membrane] | Protein | P21731 (Uniprot-TrEMBL) | |
| TRH(114-116)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRH(135-137)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRH(152-154)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRH(186-188)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRH(227-229)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRH(84-86)
[extracellular region] | Protein | P20396 (Uniprot-TrEMBL) | |
| TRHR [plasma membrane] | Protein | P34981 (Uniprot-TrEMBL) | |
| TRIO [cytosol] | Protein | O75962 (Uniprot-TrEMBL) | |
| TRIO family RhoGEFs | Protein | REACT_20038 (Reactome) | |
| TXA2 [extracellular region] | Metabolite | CHEBI:15627 (ChEBI) | |
| UDP [extracellular region] | Metabolite | CHEBI:17659 (ChEBI) | |
| UTS2(114-124)
[extracellular region] | Protein | O95399 (Uniprot-TrEMBL) | |
| UTS2B(112-119)
[extracellular region] | Protein | Q765I0 (Uniprot-TrEMBL) | |
| UTS2R [plasma membrane] | Protein | Q9UKP6 (Uniprot-TrEMBL) | |
| Valerate
[extracellular region] | Metabolite | CHEBI:31011 (ChEBI) | |
| XCL1 [extracellular region] | Protein | P47992 (Uniprot-TrEMBL) | |
| XCL2 [extracellular region] | Protein | Q9UBD3 (Uniprot-TrEMBL) | |
| XCR1 [plasma membrane] | Protein | P46094 (Uniprot-TrEMBL) | |
| p-6Y-EGFR [plasma membrane] | Protein | P00533 (Uniprot-TrEMBL) | |
| p-ERK1/2/5 | Protein | REACT_13301 (Reactome) | |
| p-S133-CREB1 | Protein | P16220 (Uniprot-TrEMBL) | |
| p21 RAS:GDP | Complex | REACT_2657 (Reactome) | |
| p21 RAS:GTP | Complex | REACT_4782 (Reactome) | |
| thrombin heavy chain
[extracellular region] | Protein | P00734 (Uniprot-TrEMBL) | |
| thrombin light chain
[extracellular region] | Protein | P00734 (Uniprot-TrEMBL) |
Annotated Interactions
| View all... |
| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| ADP | Arrow | REACT_12487 (Reactome) | ||
| ADP | Arrow | REACT_12622 (Reactome) | ||
| ADRBK1(2-689) | REACT_19213 (Reactome) | |||
| ATP | REACT_12487 (Reactome) | |||
| ATP | REACT_12622 (Reactome) | |||
| CCKBR | REACT_121113 (Reactome) | |||
| CREB1 | REACT_12622 (Reactome) | |||
| DAG | Arrow | REACT_960 (Reactome) | ||
| DAG | REACT_18303 (Reactome) | |||
| EGFR | REACT_121381 (Reactome) | |||
| G-protein alpha (q):GRK2 | Arrow | REACT_19213 (Reactome) | ||
| G-protein alpha (q):GRK5 | Arrow | REACT_19325 (Reactome) | ||
| G-protein alpha (q/11): GTP | Arrow | REACT_22263 (Reactome) | ||
| G-protein alpha (q/11): GTP | REACT_19172 (Reactome) | |||
| G-protein alpha (q/11): GTP | REACT_19186 (Reactome) | |||
| G-protein alpha (q/11): GTP | REACT_19213 (Reactome) | |||
| G-protein alpha (q/11): GTP | REACT_19270 (Reactome) | |||
| G-protein alpha (q/11): GTP | REACT_19301 (Reactome) | |||
| G-protein alpha (q/11): GTP | REACT_19325 (Reactome) | |||
| G-protein alpha (q/11):GDP | Arrow | REACT_19186 (Reactome) | ||
| G-protein alpha (q/11):GDP | REACT_22425 (Reactome) | |||
| G-protein alpha (q/11):PI3K alpha | Arrow | REACT_19172 (Reactome) | ||
| G-protein alpha
(q/11):Trio family RhoGEFs | Arrow | REACT_19301 (Reactome) | ||
| G-protein alpha (q/11) | mim-catalysis | REACT_19186 (Reactome) | ||
| G-protein beta-gamma complex | Arrow | REACT_22263 (Reactome) | ||
| G-protein beta-gamma complex | REACT_22425 (Reactome) | |||
| GAST(76-92) | REACT_121113 (Reactome) | |||
| GDP | Arrow | REACT_121377 (Reactome) | ||
| GDP | Arrow | REACT_15291 (Reactome) | ||
| GPCRs that activate Gq/11 | Arrow | REACT_22263 (Reactome) | ||
| GRB2:SOS1:HB-EGF:p-6Y-EGFR | Arrow | REACT_121250 (Reactome) | ||
| GRB2:SOS1:HB-EGF:p-6Y-EGFR | mim-catalysis | REACT_121377 (Reactome) | ||
| GRB2:SOS1 | REACT_121250 (Reactome) | |||
| GRK5 | REACT_19325 (Reactome) | |||
| GTP | REACT_121377 (Reactome) | |||
| GTP | REACT_15291 (Reactome) | |||
| Gastrin:CCKBR | Arrow | REACT_121113 (Reactome) | ||
| HB-EGF:p-6Y-EGFR dimer | Arrow | REACT_121381 (Reactome) | ||
| HB-EGF:p-6Y-EGFR dimer | REACT_121250 (Reactome) | |||
| HBEGF(149-208) | Arrow | REACT_121027 (Reactome) | ||
| HBEGF(20-208) | REACT_121027 (Reactome) | |||
| HBEGF(20-62) | Arrow | REACT_121027 (Reactome) | ||
| HBEGF(63-148) | Arrow | REACT_121027 (Reactome) | ||
| HBEGF(63-148) | REACT_121381 (Reactome) | |||
| Heterotrimeric
G-protein Gq/11 (inactive) | Arrow | REACT_22425 (Reactome) | ||
| Heterotrimeric
G-protein Gq/11 (inactive) | REACT_22436 (Reactome) | |||
| I(1,4,5)P3 | Arrow | REACT_960 (Reactome) | ||
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (active) | Arrow | REACT_15291 (Reactome) | ||
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (active) | REACT_22263 (Reactome) | |||
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (inactive) | Arrow | REACT_22436 (Reactome) | ||
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (inactive) | REACT_15291 (Reactome) | |||
| Ligand:GPCR
complexes that activate Gq/11:Heterotrimeric G-protein Gq (inactive) | mim-catalysis | REACT_15291 (Reactome) | ||
| Ligand:GPCR
complexes that activate Gq/11 | REACT_22436 (Reactome) | |||
| Ligands of GPCRs that activate Gq/11 | Arrow | REACT_22263 (Reactome) | ||
| MMP3 | Arrow | REACT_120731 (Reactome) | ||
| MMP3 | mim-catalysis | REACT_121027 (Reactome) | ||
| PI(4,5)P2 | REACT_960 (Reactome) | |||
| PI3K alpha | REACT_19172 (Reactome) | |||
| PLC beta:G alpha (q/11) | Arrow | REACT_19270 (Reactome) | ||
| PLC beta:G alpha (q/11) | mim-catalysis | REACT_960 (Reactome) | ||
| PLC-beta | REACT_19270 (Reactome) | |||
| PRKCA | REACT_18303 (Reactome) | |||
| Phospho-Ribosomal protein S6 kinase | Arrow | REACT_12487 (Reactome) | ||
| Phospho-Ribosomal protein S6 kinase | mim-catalysis | REACT_12622 (Reactome) | ||
| Protein Kinase C, alpha type: DAG | Arrow | REACT_18303 (Reactome) | ||
| Protein Kinase C, alpha type: DAG | mim-catalysis | REACT_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 (q) | Arrow | REACT_19186 (Reactome) | ||
| Ribosomal protein S6 kinase | REACT_12487 (Reactome) | |||
| TRIO family RhoGEFs | REACT_19301 (Reactome) | |||
| p-ERK1/2/5 | mim-catalysis | REACT_12487 (Reactome) | ||
| p-S133-CREB1 | Arrow | REACT_12622 (Reactome) | ||
| p21 RAS:GDP | REACT_121377 (Reactome) | |||
| p21 RAS:GTP | Arrow | REACT_121377 (Reactome) |
