Signal amplification (Homo sapiens)

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53, 117, 1231514142, 133948, 12136412410G-protein alpha(q/11) [plasmamembrane]G-protein alpha(q/11): GTP [plasmamembrane]TPreceptor:ThromboxaneA2:G-protein G13(active) [plasmamembrane]ADP:P2Y purinoceptor1 [plasma membrane]TPreceptor:ThromboxaneA2 [plasma membrane]G-protein alpha(i):GDP [plasmamembrane]ADP:P2Y purinoceptor1:G-protein Gq(inactive) [plasmamembrane]G-protein alpha(q/11) [plasmamembrane]HeterotrimericG-protein Gi(inactive) [plasmamembrane]HeterotrimericG-protein Gq(active) [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]TPreceptor:ThromboxaneA2 [plasma membrane]ADP:P2Y purinoceptor1:G-protein Gq(active) [plasmamembrane]G-protein alpha (i)[plasma membrane]G-protein alpha(q/11) [plasmamembrane]G-protein alpha (i)[plasma membrane]G-protein alpha(i):GDP [plasmamembrane]G-protein alpha(q/11):GDP [plasmamembrane]G-protein alpha(q/11) [plasmamembrane]ADP:P2Y purinoceptor12 [plasma membrane]HeterotrimericG-protein Gq/11(inactive) [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein alpha(q/11) [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]cytosolG-protein beta-gammacomplex [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein alpha(13):GTP [plasmamembrane]ADP:P2Y purinoceptor12 [plasma membrane]TPreceptor:ThromboxaneA2:G-protein Gq(inactive) [plasmamembrane]G-protein alpha(q/11):GDP [plasmamembrane]G-protein alpha(q/11) [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]TPreceptor:ThromboxaneA2 [plasma membrane]G-protein alpha(q/11): GTP [plasmamembrane]G-protein alpha (i):GTP [plasmamembrane]HeterotrimericG-protein Gi(inactive) [plasmamembrane]HeterotrimericG-protein G13(inactive) [plasmamembrane]ADP:P2Y purinoceptor1 [plasma membrane]TPreceptor:ThromboxaneA2:G-protein G13(inactive) [plasmamembrane]G-protein alpha(q/11): GTP [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]ADP:P2Y purinoceptor12:G-protein Gi(inactive) [plasmamembrane]G-protein alpha(13):GDP [plasmamembrane]HeterotrimericG-protein Gi(active) [plasmamembrane]endoplasmic reticulum lumenTPreceptor:ThromboxaneA2:G-protein Gq(active) [plasmamembrane]HeterotrimericG-protein G13(inactive) [plasmamembrane]G-protein alpha (i):GTP [plasmamembrane]HeterotrimericG-protein Gq/11(inactive) [plasmamembrane]TPreceptor:ThromboxaneA2 [plasma membrane]G-protein beta-gammacomplex [plasmamembrane]G-protein alpha (i)[plasma membrane]ADP:P2Y purinoceptor12 [plasma membrane]HeterotrimericG-protein G13(active) [plasmamembrane]HeterotrimericG-protein Gq/11(inactive) [plasmamembrane]G-protein alpha(13):GDP [plasmamembrane]G-protein alpha(13):GTP [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]ADP:P2Y purinoceptor1 [plasma membrane]G-protein alpha(q/11):GDP [plasmamembrane]TPreceptor:ThromboxaneA2 [plasma membrane]HeterotrimericG-protein Gq(active) [plasmamembrane]G-protein alpha (i)[plasma membrane]ADP:P2Y purinoceptor12:G-protein Gi(active) [plasmamembrane]GNA14 [plasmamembrane]TBXA2R(1-369)[plasma membrane]GNAQ [plasmamembrane]ADP:P2Y purinoceptor12:G-protein Gi(active)GNA11 [plasmamembrane]GNA15 [plasmamembrane]GTP [plasmamembrane]ADP [plasmamembrane]TBXA2R(1-369)[plasma membrane]G-protein beta-gammacomplexGNA11 [plasmamembrane]TPreceptor:ThromboxaneA2TBXA2R(1-369)[plasma membrane]GNA14 [plasmamembrane]GDP [plasmamembrane]G-protein alpha(13):GTPTPreceptor:ThromboxaneA2:G-protein G13(active)P2RY12GNA11 [plasmamembrane]HeterotrimericG-protein G13(inactive)ADP:P2Y purinoceptor12:G-protein Gi(inactive)ADP [plasmamembrane]GNA13 [plasmamembrane]TPreceptor:ThromboxaneA2:G-protein G13(inactive)GNA14 [plasmamembrane]ADPp-S505,S727-PLA2G4AGDP [plasmamembrane]GNAQ [plasmamembrane]GDPATPGTPGNA11 [plasmamembrane]ADPTBXA2R(1-369)[plasma membrane]G-protein alpha (i):GTPP2RY1 [plasmamembrane]GDPGNAQ [plasmamembrane]p-Y419-SRC-1GNAI3(2-354) [plasmamembrane]ADP:P2Y purinoceptor1:G-protein Gq(active)GNA14 [plasmamembrane]GNA15 [plasmamembrane]GTPTXA2 [extracellularregion]TPreceptor:ThromboxaneA2:G-protein Gq(inactive)GNAT3(2-354) [plasmamembrane]GDP [plasmamembrane]GNA15 [plasmamembrane]TBXA2R(1-369)[plasma membrane]ADP:P2Y purinoceptor12GNAI3(2-354) [plasmamembrane]GNAI1(2-354) [plasmamembrane]GNAQ [plasmamembrane]GNA15 [plasmamembrane]TPreceptor:ThromboxaneA2:G-protein Gq(active)GTP [plasmamembrane]GNAI1(2-354) [plasmamembrane]GTP [plasmamembrane]HeterotrimericG-protein Gq/11(inactive)GNA11 [plasmamembrane]PLA2G4ATXA2 [extracellularregion]P2RY12 [plasmamembrane]GTP [plasmamembrane]GNA15 [plasmamembrane]MAPK14GTP [plasmamembrane]P2RY12 [plasmamembrane]GTP [plasmamembrane]ADP [plasmamembrane]TXA2 [extracellularregion]HeterotrimericG-protein Gi(inactive)GNA13 [plasmamembrane]GNAT3(2-354) [plasmamembrane]P2RY1 [plasmamembrane]GNAQ [plasmamembrane]GDPP2RY1G-protein alpha(q/11): GTPGNAI3(2-354) [plasmamembrane]GNAQ [plasmamembrane]GNAT3(2-354) [plasmamembrane]ADP [plasmamembrane]GDPGDP [plasmamembrane]GNAI3(2-354) [plasmamembrane]GNA11 [plasmamembrane]ADP [plasmamembrane]SRC-1GDP [plasmamembrane]GNAI1(2-354) [plasmamembrane]ATPTXA2GTPGTP [plasmamembrane]p-T180,Y182-MAPK14ADP:P2Y purinoceptor1:G-protein Gq(inactive)GNAT3(2-354) [plasmamembrane]ADP [plasmamembrane]GDP [plasmamembrane]GNA14 [plasmamembrane]TBXA2R(1-369)GNA13 [plasmamembrane]GNA15 [plasmamembrane]GDP [plasmamembrane]GNAI2(2-355) [plasmamembrane]P2RY1 [plasmamembrane]GNAI1(2-354) [plasmamembrane]GNAI2(2-355) [plasmamembrane]TXA2 [extracellularregion]ADPGNA13 [plasmamembrane]GNAI2(2-355) [plasmamembrane]ADP:P2Y purinoceptor1ADPGTPGNA14 [plasmamembrane]TXA2 [extracellularregion]P2RY12 [plasmamembrane]GNAI2(2-355) [plasmamembrane]


Description

In the initial response to injury, platelets adhere to damaged blood vessels, responding to the exposure of collagen from the vascular epithelium. Once adhered they degranulate, releasing stored secondary agents such as ADP and ATP, and synthesized thromboxane A2. These amplify the response, activating and recruiting further platelets to the area and promoting platelet aggregation. Adenosine nucleotides secreted following platelet activation signal through P2 purinergic receptors on the platelet membrane. ADP activates P2Y1 and P2Y12 while ATP activates the ionotropic P2X1 receptor (Kunapuli et al. 2003). Activation of these receptors initiates a complex signaling cascade that ultimately results in platelet activation and thrombus formation (Kahner et al. 2006). ADP stimulation of P2Y1 and P2Y12 involves signaling via both the alpha and gamma:beta components of the heterotrimeric G-protein (Hirsch et al. 2001, 2006).Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=392518

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Bibliography

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  1. Hardy AR, Jones ML, Mundell SJ, Poole AW.; ''Reciprocal cross-talk between P2Y1 and P2Y12 receptors at the level of calcium signaling in human platelets.''; PubMed Europe PMC Scholia
  2. Léon C, Vial C, Cazenave JP, Gachet C.; ''Cloning and sequencing of a human cDNA encoding endothelial P2Y1 purinoceptor.''; PubMed Europe PMC Scholia
  3. Schachter JB, Li Q, Boyer JL, Nicholas RA, Harden TK.; ''Second messenger cascade specificity and pharmacological selectivity of the human P2Y1-purinoceptor.''; PubMed Europe PMC Scholia
  4. Kramer RM, Roberts EF, Um SL, Börsch-Haubold AG, Watson SP, Fisher MJ, Jakubowski JA.; ''p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets. Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2.''; PubMed Europe PMC Scholia
  5. Chou KC.; ''Coupling interaction between thromboxane A2 receptor and alpha-13 subunit of guanine nucleotide-binding protein.''; PubMed Europe PMC Scholia
  6. Lambert NA.; ''Dissociation of heterotrimeric g proteins in cells.''; PubMed Europe PMC Scholia
  7. Davì G, Patrono C.; ''Platelet activation and atherothrombosis.''; PubMed Europe PMC Scholia
  8. Kinsella BT, O'Mahony DJ, Fitzgerald GA.; ''The human thromboxane A2 receptor alpha isoform (TP alpha) functionally couples to the G proteins Gq and G11 in vivo and is activated by the isoprostane 8-epi prostaglandin F2 alpha.''; PubMed Europe PMC Scholia
  9. Dangelmaier C, Jin J, Daniel JL, Smith JB, Kunapuli SP.; ''The P2Y1 receptor mediates ADP-induced p38 kinase-activating factor generation in human platelets.''; PubMed Europe PMC Scholia
  10. Hirata M, Hayashi Y, Ushikubi F, Yokota Y, Kageyama R, Nakanishi S, Narumiya S.; ''Cloning and expression of cDNA for a human thromboxane A2 receptor.''; PubMed Europe PMC Scholia
  11. Shenker A, Goldsmith P, Unson CG, Spiegel AM.; ''The G protein coupled to the thromboxane A2 receptor in human platelets is a member of the novel Gq family.''; PubMed Europe PMC Scholia
  12. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB.; ''Identification of the platelet ADP receptor targeted by antithrombotic drugs.''; PubMed Europe PMC Scholia
  13. Bodor ET, Waldo GL, Hooks SB, Corbitt J, Boyer JL, Harden TK.; ''Purification and functional reconstitution of the human P2Y12 receptor.''; PubMed Europe PMC Scholia
  14. Ohlmann P, Laugwitz KL, Nürnberg B, Spicher K, Schultz G, Cazenave JP, Gachet C.; ''The human platelet ADP receptor activates Gi2 proteins.''; PubMed Europe PMC Scholia
  15. Schachter JB, Sromek SM, Nicholas RA, Harden TK.; ''HEK293 human embryonic kidney cells endogenously express the P2Y1 and P2Y2 receptors.''; PubMed Europe PMC Scholia
  16. Zhang L, DiLizio C, Kim D, Smyth EM, Manning DR.; ''The G12 family of G proteins as a reporter of thromboxane A2 receptor activity.''; PubMed Europe PMC Scholia
  17. Reid HM, Wikström K, Kavanagh DJ, Mulvaney EP, Kinsella BT.; ''Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A₂ receptor.''; PubMed Europe PMC Scholia
  18. Waldo GL, Harden TK.; ''Agonist binding and Gq-stimulating activities of the purified human P2Y1 receptor.''; PubMed Europe PMC Scholia
  19. Ding Z, Kim S, Dorsam RT, Jin J, Kunapuli SP.; ''Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114772view16:26, 25 January 2021ReactomeTeamReactome version 75
113216view11:28, 2 November 2020ReactomeTeamReactome version 74
112440view15:38, 9 October 2020ReactomeTeamReactome version 73
101345view11:23, 1 November 2018ReactomeTeamreactome version 66
100883view20:57, 31 October 2018ReactomeTeamreactome version 65
100424view19:31, 31 October 2018ReactomeTeamreactome version 64
99973view16:15, 31 October 2018ReactomeTeamreactome version 63
99528view14:51, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99167view12:42, 31 October 2018ReactomeTeamreactome version 62
93937view13:46, 16 August 2017ReactomeTeamreactome version 61
93526view11:26, 9 August 2017ReactomeTeamreactome version 61
86625view09:22, 11 July 2016ReactomeTeamreactome version 56
83050view09:47, 18 November 2015ReactomeTeamVersion54
81353view12:52, 21 August 2015ReactomeTeamVersion53
76822view08:04, 17 July 2014ReactomeTeamFixed remaining interactions
76526view11:45, 16 July 2014ReactomeTeamFixed remaining interactions
75859view09:51, 11 June 2014ReactomeTeamRe-fixing comment source
75559view10:35, 10 June 2014ReactomeTeamReactome 48 Update
74914view13:44, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74558view08:35, 30 April 2014ReactomeTeamReactome46
45229view17:42, 7 October 2011KhanspersOntology Term : 'G protein mediated signaling pathway' added !
45228view17:41, 7 October 2011KhanspersOntology Term : 'platelet aggregation pathway' added !
45227view17:40, 7 October 2011KhanspersOntology Term : 'platelet' added !
42124view21:58, 4 March 2011MaintBotAutomatic update
39934view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADP [plasma membrane]MetaboliteCHEBI:16761 (ChEBI)
ADP:P2Y purinoceptor

12:G-protein Gi

(active)		ComplexREACT_20967 (Reactome)
ADP:P2Y purinoceptor

12:G-protein Gi

(inactive)		ComplexREACT_21024 (Reactome)
ADP:P2Y purinoceptor 12ComplexREACT_20705 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(active)		ComplexREACT_20825 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(inactive)		ComplexREACT_21114 (Reactome)
ADP:P2Y purinoceptor 1ComplexREACT_21127 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
G-protein alpha (13):GTPComplexREACT_18118 (Reactome)
G-protein alpha (q/11): GTPComplexREACT_5863 (Reactome)
G-protein alpha (i): GTPComplexREACT_19580 (Reactome)
G-protein beta-gamma complexComplexREACT_15674 (Reactome)
GDP [plasma membrane]MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNA11 [plasma membrane]ProteinP29992 (Uniprot-TrEMBL)
GNA13 [plasma membrane]ProteinQ14344 (Uniprot-TrEMBL)
GNA14 [plasma membrane]ProteinO95837 (Uniprot-TrEMBL)
GNA15 [plasma membrane]ProteinP30679 (Uniprot-TrEMBL)
GNAI1(2-354) [plasma membrane]ProteinP63096 (Uniprot-TrEMBL)
GNAI2(2-355) [plasma membrane]ProteinP04899 (Uniprot-TrEMBL)
GNAI3(2-354) [plasma membrane]ProteinP08754 (Uniprot-TrEMBL)
GNAQ [plasma membrane]ProteinP50148 (Uniprot-TrEMBL)
GNAT3(2-354) [plasma membrane]ProteinA8MTJ3 (Uniprot-TrEMBL)
GTP [plasma membrane]MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Heterotrimeric

G-protein G13

(inactive)		ComplexREACT_17830 (Reactome)
Heterotrimeric

G-protein Gi

(inactive)		ComplexREACT_20935 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)		ComplexREACT_5130 (Reactome)
MAPK14ProteinQ16539 (Uniprot-TrEMBL)
P2RY1 [plasma membrane]ProteinP47900 (Uniprot-TrEMBL)
P2RY12 [plasma membrane]ProteinQ9H244 (Uniprot-TrEMBL)
P2RY12ProteinQ9H244 (Uniprot-TrEMBL)
P2RY1ProteinP47900 (Uniprot-TrEMBL)
PLA2G4AProteinP47712 (Uniprot-TrEMBL)
SRC-1ProteinP12931-1 (Uniprot-TrEMBL)
TBXA2R(1-369) [plasma membrane]ProteinP21731 (Uniprot-TrEMBL)
TBXA2R(1-369)ProteinP21731 (Uniprot-TrEMBL)
TP

receptor:Thromboxane A2:G-protein G13

(active)		ComplexREACT_20781 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(inactive)		ComplexREACT_20823 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(active)		ComplexREACT_20944 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(inactive)		ComplexREACT_20867 (Reactome)
TP

receptor:Thromboxane

A2		ComplexREACT_18599 (Reactome)
TXA2 [extracellular region]MetaboliteCHEBI:15627 (ChEBI)
TXA2MetaboliteCHEBI:15627 (ChEBI)
p-S505,S727-PLA2G4AProteinP47712 (Uniprot-TrEMBL)
p-T180,Y182-MAPK14ProteinQ16539 (Uniprot-TrEMBL)
p-Y419-SRC-1ProteinP12931-1 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADP:P2Y purinoceptor

12:G-protein Gi

(active)		ArrowREACT_20507 (Reactome)
ADP:P2Y purinoceptor

12:G-protein Gi

(active)		REACT_20630 (Reactome)
ADP:P2Y purinoceptor

12:G-protein Gi

(inactive)		ArrowREACT_20523 (Reactome)
ADP:P2Y purinoceptor

12:G-protein Gi

(inactive)		REACT_20507 (Reactome)
ADP:P2Y purinoceptor

12:G-protein Gi

(inactive)		mim-catalysisREACT_20507 (Reactome)
ADP:P2Y purinoceptor 12ArrowREACT_20574 (Reactome)
ADP:P2Y purinoceptor 12REACT_20523 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(active)		ArrowREACT_20636 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(active)		REACT_20551 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(inactive)		ArrowREACT_20525 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(inactive)		REACT_20636 (Reactome)
ADP:P2Y purinoceptor

1:G-protein Gq

(inactive)		mim-catalysisREACT_20636 (Reactome)
ADP:P2Y purinoceptor 1ArrowREACT_20590 (Reactome)
ADP:P2Y purinoceptor 1REACT_20525 (Reactome)
ADPArrowREACT_20541 (Reactome)
ADPArrowREACT_20551 (Reactome)
ADPArrowREACT_20630 (Reactome)
ADPArrowREACT_20632 (Reactome)
ADPREACT_20574 (Reactome)
ADPREACT_20590 (Reactome)
ATPREACT_20541 (Reactome)
ATPREACT_20632 (Reactome)
G-protein alpha (13):GTPArrowREACT_20559 (Reactome)
G-protein alpha (q/11): GTPArrowREACT_20551 (Reactome)
G-protein alpha (q/11): GTPArrowREACT_20658 (Reactome)
G-protein alpha (q/11): GTPmim-catalysisREACT_20632 (Reactome)
G-protein alpha (i): GTPArrowREACT_20630 (Reactome)
G-protein beta-gamma complexArrowREACT_20551 (Reactome)
G-protein beta-gamma complexArrowREACT_20559 (Reactome)
G-protein beta-gamma complexArrowREACT_20630 (Reactome)
G-protein beta-gamma complexArrowREACT_20658 (Reactome)
GDPArrowREACT_20507 (Reactome)
GDPArrowREACT_20511 (Reactome)
GDPArrowREACT_20567 (Reactome)
GDPArrowREACT_20636 (Reactome)
GTPREACT_20507 (Reactome)
GTPREACT_20511 (Reactome)
GTPREACT_20567 (Reactome)
GTPREACT_20636 (Reactome)
Heterotrimeric

G-protein G13

(inactive)		REACT_20501 (Reactome)
Heterotrimeric

G-protein Gi

(inactive)		REACT_20523 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)		REACT_20520 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)		REACT_20525 (Reactome)
MAPK14REACT_20632 (Reactome)
P2RY12ArrowREACT_20630 (Reactome)
P2RY12REACT_20574 (Reactome)
P2RY1ArrowREACT_20551 (Reactome)
P2RY1REACT_20590 (Reactome)
PLA2G4AREACT_20541 (Reactome)
REACT_18364 (Reactome) Thromboxane (TBXA2) is a potent stimulator for platelet aggregation and clot formation and also plays a role in vascular tone. The thromboxane receptor TP (Hirata et al. 1991) is found on the surface of vascular endothelium, platelets and in the placenta. Once bound to its ligand, TP's effects are mediated via coupling to G q/11 activation of a phosphatidylinositol-calcium second messenger system (Kinsella BT et al, 1997). TP signaling also involves G12/13 signaling; selective activation of G12/13 results in dense granule release in a mechanism that is independent of Gq/phospholipase C. The downstream mechanism for this is thought to be RhoA mediated activation of PKCdelta, as PAR-mediated dense granule release is inhibited if RhoA is blocked, and RhoA regulates PKCdelta T505 phosphorylation (Jin et al. 2009).
REACT_20501 (Reactome) The thromboxane receptor (TP) can activate G12 and G13.
REACT_20507 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
REACT_20511 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
REACT_20520 (Reactome) The TP receptor can activate Gq leading to stimulation of Phospholipase C and consequent increase in intracellular calcium.
REACT_20523 (Reactome) The activated receptor binds the inactive, GDP-bound form of the heterotrimeric G-protein Gi.
REACT_20525 (Reactome) P2Y1 is coupled to the Gq family of G protein alpha subunits, causing increases in intracellular calcium concentration through stimulation of PLC.
REACT_20541 (Reactome) MAPK p38 alpha activates cPLA2 by phosphorylation of two serine residues.
cPLA2 can be phosphorylated and activated by ERK2 (Lin et al. 1993), and were believed to be responsible for the phosphorylation of cPLA2. However, phosphorylation of cPLA2 occurred in the absence of ERK activation in human platelets stimulated with the thrombin receptor agonist peptide SFLLRN (Kramer et al. 1995), and cPLA2 phosphorylation induced by thrombin or collagen was unaffected by PKC inhibitors that prevent ERK activation (Börsch-Haubold et al. 1995). In addition, a specific inhibitor of ERKs did not block thrombin-induced cPLA2 phosphorylation (Börsch-Haubold et al. 1996).
REACT_20551 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (s) 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_20559 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (s) 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_20567 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
REACT_20574 (Reactome) P2RY12 is one of two ADP receptors expressed in platelets. P2Y12 activation leads to irreversible platelet aggregation. Defects in this receptor are associated with bleeding disorders.
REACT_20585 (Reactome) Activation of Src lies selectively downstream of P2Y1, but not P2Y12. The precise mechanism is not known, but Src regulation of the PI3K component of the intracellular calcium response downstream of P2Y12 represents a point of reciprocal cross-talk between P2Y1 and P2Y12 receptors.
REACT_20590 (Reactome) Two platelet ADP receptors, P2Y1 and P2Y12, initiate platelet activation when stimulated in concert. Both are heterotrimeric G-protein-coupled receptors; P2Y1 signals through Gq while P2Y12 signals through Gi. Stimulation of P2Y1 leads to intracellular calcium mobilization and platelet shape change.
REACT_20630 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (s) 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_20632 (Reactome) ADP activates human platelets and induces endothelial cell migration. These effects are partly mediated by the P2Y1 purinocetor, inducing p38 MAP kinase activation via an uncharacterised factor. Possible mechanisms include flotillin-mediated stimulation of SRC family kinases in lipid rafts (Sugawara et al. 2007).
REACT_20636 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
REACT_20658 (Reactome) The classical view of G-protein signalling is that the G-protein alpha subunit dissociates from the beta:gamma dimer. Activated G alpha (s) 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).
SRC-1REACT_20585 (Reactome)
TBXA2R(1-369)ArrowREACT_20559 (Reactome)
TBXA2R(1-369)ArrowREACT_20658 (Reactome)
TBXA2R(1-369)REACT_18364 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(active)		ArrowREACT_20567 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(active)		REACT_20559 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(inactive)		ArrowREACT_20501 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(inactive)		REACT_20567 (Reactome)
TP

receptor:Thromboxane A2:G-protein G13

(inactive)		mim-catalysisREACT_20567 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(active)		ArrowREACT_20511 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(active)		REACT_20658 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(inactive)		ArrowREACT_20520 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(inactive)		REACT_20511 (Reactome)
TP

receptor:Thromboxane A2:G-protein Gq

(inactive)		mim-catalysisREACT_20511 (Reactome)
TP

receptor:Thromboxane

A2		ArrowREACT_18364 (Reactome)
TP

receptor:Thromboxane

A2		REACT_20501 (Reactome)
TP

receptor:Thromboxane

A2		REACT_20520 (Reactome)
TXA2ArrowREACT_20559 (Reactome)
TXA2ArrowREACT_20658 (Reactome)
TXA2REACT_18364 (Reactome)
p-S505,S727-PLA2G4AArrowREACT_20541 (Reactome)
p-T180,Y182-MAPK14ArrowREACT_20632 (Reactome)
p-T180,Y182-MAPK14mim-catalysisREACT_20541 (Reactome)
p-Y419-SRC-1ArrowREACT_20585 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1908"
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