Signal amplification (Homo sapiens)

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113177115, 168, 1286, 8, 1033145, 151532413, 179, 18cytosolendoplasmic reticulum lumenGNG13 GNB5 P2RY12:ADPGNG7 GNB1 GNA11 GNG4 GNG3 TBXA2R ADP GNB1 GNB4 GNB5 ADPGNAI2 GNGT1 GNB3 GDP GNB2 GNAI3 TBXA2R TXA2 GNGT1 GNG12 GNG12 TPreceptor:Thromboxane A2:G-protein Gq (active)GNA15 TPreceptor:Thromboxane A2:G-protein Gq (inactive)GNGT1 P2RY1GNG11 GNAI1 GNB5 GNG3 GNG12 GNA14 TBXA2R GNG12 GNG8 GNA14 GDP GDPADPGNG10 GNG10 GNGT2 GNB4 GNB2 GNG10 GNB4 GNG3 TXA2 ADP:P2RY12:G-proteinGi (inactive)GNG7 GNG4 GNG7 GNG12 GNB5 ADP GNA11 GNB4 GTP GNG5 GNB4 GNG2 GNG10 GNG2 GNAI3 GNG3 GNB2 GNB1 GNG13 ADP GNG5 GNG7 GNGT2 GNA15 GNG4 GNG5 GNG7 GNA13 ADP:P2RY1:G-proteinGq (active)GNB4 GNAI2 GNA14 GNB4 GNB3 GNB5 GNG4 GNG3 GNAI1 p-S505,S727-PLA2G4AGNG12 GTP P2RY1 TXA2GNB2 GNB3 GNG12 GNG5 GNB2 GNG8 GNB2 GNA11 GNAI1 GNG10 GNB1 GTPG-protein alpha(13):GTPGNG8 GNG7 GNG12 GNGT2 GNG4 p-T180,Y182-MAPK14GNG2 GNB3 GDPGNG12 GNAI1 GNG10 ADPTPreceptor:Thromboxane A2:G-protein G13 (active)GNG5 GNB1 GNG13 GNB3 GNG2 GNG5 GNB1 GNA15 GTP GNG7 GNG12 GTP GNG12 GNG3 GTP GNG13 GNGT1 GNG13 GNAQ GDP GNG4 GNG5 GNG7 GNB5 GNG11 GNGT1 TXA2 GNG7 GNG2 GNGT1 ADP:P2RY1:G-proteinGq/11 (inactive)GTP GNB5 GNAI2 TBXA2R G-protein beta-gammacomplexGTPTXA2 GNAQ GNG13 GNAQ ATPTXA2 GDPHeterotrimericG-protein G13(inactive)GNA11 MAPK14GNG7 GNAQ GNB1 GNB2 GNG8 GNA14 GNAI2 SRC-1GNG8 GNG13 GNAT3 GNA11 GNG11 GNB2 ADP GNB1 GDP GNG3 GNGT1 GNG2 GNG11 GNA11 GNGT2 GNA13 GNA13 ADP GNG8 TBXA2R GNAI3 HeterotrimericG-protein Gi(inactive)GNG2 GNB1 GNG10 GNG13 GNGT1 GNB5 GNG10 GNG11 PLA2G4AGNA15 GNB4 GNGT2 P2RY12 GNG8 GNAQ GNB3 GNG13 GNB5 P2RY1 GNG2 GNG13 GTP P2RY12p-Y419-SRCGNG8 GNB5 GNGT1 GNG4 GNG2 GNA15 GNGT2 GNG2 ATPGNG8 GNGT1 GNGT1 GNAT3 GNG4 TBXA2R:TXA2GNGT2 GNB2 GNGT2 GNG5 GNB5 GNG5 GNG11 GNA14 GDPGNGT2 GNG8 GNG4 GNG8 GNG13 HeterotrimericG-protein Gq/11(inactive)GNGT2 ADP GTPGNG5 G-protein alpha(q/11): GTPG alpha (i): GTPGNB3 GNB1 GNGT1 GNAI3 GNG11 GNB4 GNG10 GNG4 GNG10 GNG10 GNG3 GNG11 GNB4 GNG3 GNG3 GNA14 P2RY12 GNB5 GNG11 GNB2 GNAT3 GNG4 GNAQ GNG12 GNB2 GNG3 GDP ADPGNGT2 GNG2 GNG2 GDP GNG11 GNG5 P2RY1:ADPGNA15 GNB4 GNG11 GNB2 GNG4 P2RY12 GNG11 GDP TBXA2RGNB3 GNB4 GNG10 GNG7 GNG5 GTPADP:P2RY12:G-proteinGi (active)GNB3 GNG3 GNG7 GNB1 GNGT2 GNAT3 GNB3 TPreceptor:Thromboxane A2:G-protein G13 (inactive)GNB3 GNG8 P2RY1 GNB1 GNG13 GNA13 GNB3


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). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 392518
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Akkerman, Jan Willem N

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Bibliography

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  1. 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
  2. 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
  3. Lambert NA.; ''Dissociation of heterotrimeric g proteins in cells.''; PubMed Europe PMC
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. Léon C, Vial C, Cazenave JP, Gachet C.; ''Cloning and sequencing of a human cDNA encoding endothelial P2Y1 purinoceptor.''; PubMed Europe PMC
  10. Bodor ET, Waldo GL, Hooks SB, Corbitt J, Boyer JL, Harden TK.; ''Purification and functional reconstitution of the human P2Y12 receptor.''; PubMed Europe PMC
  11. Davì G, Patrono C.; ''Platelet activation and atherothrombosis.''; PubMed Europe PMC
  12. 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
  13. Chou KC.; ''Coupling interaction between thromboxane A2 receptor and alpha-13 subunit of guanine nucleotide-binding protein.''; PubMed Europe PMC
  14. Waldo GL, Harden TK.; ''Agonist binding and Gq-stimulating activities of the purified human P2Y1 receptor.''; PubMed Europe PMC
  15. 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
  16. 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
  17. 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
  18. Schachter JB, Sromek SM, Nicholas RA, Harden TK.; ''HEK293 human embryonic kidney cells endogenously express the P2Y1 and P2Y2 receptors.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
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 MetaboliteCHEBI:16761 (ChEBI)
ADP:P2RY12:G-protein Gi (active)ComplexR-HSA-392194 (Reactome)
ADP:P2RY12:G-protein Gi (inactive)ComplexR-HSA-392184 (Reactome)
ADP:P2RY1:G-protein Gq (active)ComplexR-HSA-418575 (Reactome)
ADP:P2RY1:G-protein Gq/11 (inactive)ComplexR-HSA-418578 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
G alpha (i): GTPComplexR-HSA-392161 (Reactome)
G-protein alpha (13):GTPComplexR-HSA-398056 (Reactome)
G-protein alpha (q/11): GTPComplexR-HSA-114534 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNA11 ProteinP29992 (Uniprot-TrEMBL)
GNA13 ProteinQ14344 (Uniprot-TrEMBL)
GNA14 ProteinO95837 (Uniprot-TrEMBL)
GNA15 ProteinP30679 (Uniprot-TrEMBL)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAQ ProteinP50148 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Heterotrimeric

G-protein G13

(inactive)
ComplexR-HSA-398072 (Reactome)
Heterotrimeric

G-protein Gi

(inactive)
ComplexR-HSA-392165 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)
ComplexR-HSA-114557 (Reactome)
MAPK14ProteinQ16539 (Uniprot-TrEMBL)
P2RY1 ProteinP47900 (Uniprot-TrEMBL)
P2RY12 ProteinQ9H244 (Uniprot-TrEMBL)
P2RY12:ADPComplexR-HSA-417834 (Reactome)
P2RY12ProteinQ9H244 (Uniprot-TrEMBL)
P2RY1:ADPComplexR-HSA-417920 (Reactome)
P2RY1ProteinP47900 (Uniprot-TrEMBL)
PLA2G4AProteinP47712 (Uniprot-TrEMBL)
SRC-1ProteinP12931-1 (Uniprot-TrEMBL)
TBXA2R ProteinP21731 (Uniprot-TrEMBL)
TBXA2R:TXA2ComplexR-HSA-391925 (Reactome)
TBXA2RProteinP21731 (Uniprot-TrEMBL)
TP receptor:Thromboxane A2:G-protein G13 (active)ComplexR-HSA-428907 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (inactive)ComplexR-HSA-428905 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (active)ComplexR-HSA-428904 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (inactive)ComplexR-HSA-428764 (Reactome)
TXA2 MetaboliteCHEBI:15627 (ChEBI)
TXA2MetaboliteCHEBI:15627 (ChEBI)
p-S505,S727-PLA2G4AProteinP47712 (Uniprot-TrEMBL)
p-T180,Y182-MAPK14ProteinQ16539 (Uniprot-TrEMBL)
p-Y419-SRCProteinP12931-1 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADP:P2RY12:G-protein Gi (active)ArrowR-HSA-392195 (Reactome)
ADP:P2RY12:G-protein Gi (active)R-HSA-392202 (Reactome)
ADP:P2RY12:G-protein Gi (inactive)ArrowR-HSA-392187 (Reactome)
ADP:P2RY12:G-protein Gi (inactive)R-HSA-392195 (Reactome)
ADP:P2RY12:G-protein Gi (inactive)mim-catalysisR-HSA-392195 (Reactome)
ADP:P2RY1:G-protein Gq (active)ArrowR-HSA-418579 (Reactome)
ADP:P2RY1:G-protein Gq (active)R-HSA-418576 (Reactome)
ADP:P2RY1:G-protein Gq/11 (inactive)ArrowR-HSA-418581 (Reactome)
ADP:P2RY1:G-protein Gq/11 (inactive)R-HSA-418579 (Reactome)
ADP:P2RY1:G-protein Gq/11 (inactive)mim-catalysisR-HSA-418579 (Reactome)
ADPArrowR-HSA-392202 (Reactome)
ADPArrowR-HSA-418576 (Reactome)
ADPArrowR-HSA-428941 (Reactome)
ADPArrowR-HSA-428961 (Reactome)
ADPR-HSA-417829 (Reactome)
ADPR-HSA-417908 (Reactome)
ATPR-HSA-428941 (Reactome)
ATPR-HSA-428961 (Reactome)
G alpha (i): GTPArrowR-HSA-392202 (Reactome)
G-protein alpha (13):GTPArrowR-HSA-428918 (Reactome)
G-protein alpha (q/11): GTPArrowR-HSA-418576 (Reactome)
G-protein alpha (q/11): GTPArrowR-HSA-428752 (Reactome)
G-protein alpha (q/11): GTPmim-catalysisR-HSA-428941 (Reactome)
G-protein beta-gamma complexArrowR-HSA-392202 (Reactome)
G-protein beta-gamma complexArrowR-HSA-418576 (Reactome)
G-protein beta-gamma complexArrowR-HSA-428752 (Reactome)
G-protein beta-gamma complexArrowR-HSA-428918 (Reactome)
GDPArrowR-HSA-392195 (Reactome)
GDPArrowR-HSA-418579 (Reactome)
GDPArrowR-HSA-428750 (Reactome)
GDPArrowR-HSA-428917 (Reactome)
GTPR-HSA-392195 (Reactome)
GTPR-HSA-418579 (Reactome)
GTPR-HSA-428750 (Reactome)
GTPR-HSA-428917 (Reactome)
Heterotrimeric

G-protein G13

(inactive)
R-HSA-428909 (Reactome)
Heterotrimeric

G-protein Gi

(inactive)
R-HSA-392187 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)
R-HSA-418581 (Reactome)
Heterotrimeric

G-protein Gq/11

(inactive)
R-HSA-428749 (Reactome)
MAPK14R-HSA-428941 (Reactome)
P2RY12:ADPArrowR-HSA-417829 (Reactome)
P2RY12:ADPR-HSA-392187 (Reactome)
P2RY12ArrowR-HSA-392202 (Reactome)
P2RY12R-HSA-417829 (Reactome)
P2RY1:ADPArrowR-HSA-417908 (Reactome)
P2RY1:ADPR-HSA-418581 (Reactome)
P2RY1ArrowR-HSA-418576 (Reactome)
P2RY1R-HSA-417908 (Reactome)
PLA2G4AR-HSA-428961 (Reactome)
R-HSA-391939 (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).
R-HSA-392187 (Reactome) The activated receptor binds the inactive, GDP-bound form of the heterotrimeric G-protein Gi.
R-HSA-392195 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
R-HSA-392202 (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).
R-HSA-417829 (Reactome) P2RY12 (Bodor et al. 2003) is found on the surface of blood platelet cells and is an important regulator in blood clotting. It is one of two ADP receptors expressed in platelets, the other is P2RY1. Activation leads to irreversible platelet aggregation. Defects in this receptor are associated with bleeding disorders. Its preferred ligand is ADP. The platelet anticoagulant drug clopidogrel binds to this receptor (Hollopeter G et al. 2001).
R-HSA-417908 (Reactome) P2RY1 binds ADP (Leon et al. 1996). It is one of two platelet ADP receptors, the other is P2RY12, that initiate platelet activation when stimulated in concert. P2RY1 signals through Gq, while P2Y12 signals through Gi. This results in mobilization of intracellular calcium ions via activation of phospholipase C, which leads to a change in platelet shape and probably to platelet aggregation (Schachter et al. 1997).
R-HSA-418576 (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).
R-HSA-418579 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
R-HSA-418581 (Reactome) P2Y1 is coupled to the Gq family of G protein alpha subunits, causing increases in intracellular calcium concentration through stimulation of PLC.
R-HSA-418662 (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.
R-HSA-428749 (Reactome) The TP receptor can activate Gq leading to stimulation of Phospholipase C and consequent increase in intracellular calcium.
R-HSA-428750 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
R-HSA-428752 (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).
R-HSA-428909 (Reactome) The thromboxane receptor (TP) can activate G12 and G13.
R-HSA-428917 (Reactome) The G-protein alpha subunit exchanges GDP for GTP
R-HSA-428918 (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).
R-HSA-428941 (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).
R-HSA-428961 (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).
SRC-1R-HSA-418662 (Reactome)
TBXA2R:TXA2ArrowR-HSA-391939 (Reactome)
TBXA2R:TXA2R-HSA-428749 (Reactome)
TBXA2R:TXA2R-HSA-428909 (Reactome)
TBXA2RArrowR-HSA-428752 (Reactome)
TBXA2RArrowR-HSA-428918 (Reactome)
TBXA2RR-HSA-391939 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (active)ArrowR-HSA-428917 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (active)R-HSA-428918 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (inactive)ArrowR-HSA-428909 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (inactive)R-HSA-428917 (Reactome)
TP receptor:Thromboxane A2:G-protein G13 (inactive)mim-catalysisR-HSA-428917 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (active)ArrowR-HSA-428750 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (active)R-HSA-428752 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (inactive)ArrowR-HSA-428749 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (inactive)R-HSA-428750 (Reactome)
TP receptor:Thromboxane A2:G-protein Gq (inactive)mim-catalysisR-HSA-428750 (Reactome)
TXA2ArrowR-HSA-428752 (Reactome)
TXA2ArrowR-HSA-428918 (Reactome)
TXA2R-HSA-391939 (Reactome)
p-S505,S727-PLA2G4AArrowR-HSA-428961 (Reactome)
p-T180,Y182-MAPK14ArrowR-HSA-428941 (Reactome)
p-T180,Y182-MAPK14mim-catalysisR-HSA-428961 (Reactome)
p-Y419-SRCArrowR-HSA-418662 (Reactome)
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