STANDARD_NAME BIOCARTA_SPPA_PATHWAY SYSTEMATIC_NAME M8731 COLLECTION C2:CP:BIOCARTA MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_SPPA_PATHWAY NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Aspirin Blocks Signaling Pathway Involved in Platelet Activation DESCRIPTION_FULL Activation of the protease-activated GPCRs in platelets contributes to platelet activation in clotting. The protease-activated receptors PAR1 and PAR4 are cleaved by the protease thrombin, releasing a tethered peptide ligand that activates the receptor and triggers intracellular calcium release. Platelets from mice lacking the PAR4 gene are not activated by thrombin and are impaired in clotting, supporting the importance of thrombin signaling through PAR4 in clotting. Human platelets express both PAR1 and PAR4, with PAR1 playing a more dominant role in clotting in humans. Calcium release induced by PARs activates PKC, modulating integrin alpha IIB beta 3 (glycoprotein IIb/IIIa) and opening integrin ligand binding sites to contribute to platelet aggregation. Intracellular calcium increases induced by thrombin activates phospholipase A2, liberating arachidonic acid, the first step in prostaglandin and thromboxane biosynthesis. Ras/Map kinase activation by the PAR receptors also activates phospholipase A2. The activation of PAR-induced platelet aggregation is inhibited by aspirin, indicating that thromboxane production induced by PAR signaling contributes to platelet activation. Arachidonic acid is converted to the prostaglandin PGG2 by the enzyme Cox-1 in platelets, and Cox-1 is inhibited by aspirin, reducing thromboxane A2 production by platelets. Thromboxane is a potent vasoconstrictor and platelet activator, so inhibition of Cox-1 in platelets by aspirin may explain some of the cardioprotective actions of aspirin. PMID GEOID AUTHORS CONTRIBUTOR BioCarta CONTRIBUTOR_ORG BioCarta EXACT_SOURCE FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_sppaPathway.gif SOURCE_MEMBERS AK055431,NM_000506,NM_000962,NM_001040056,NM_001061,NM_001109891,NM_001130442,NM_001130966,NM_001135052,NM_001166253,NM_001166254,NM_001174167,NM_001174168,NM_001271164,NM_001271165,NM_001271166,NM_001271367,NM_001271368,NM_001992,NM_002211,NM_002737,NM_002738,NM_002745,NM_002746,NM_002755,NM_002880,NM_003177,NM_003950,NM_005343,NM_015192,NM_024420,NM_030984,NM_033668,NM_080591,NM_133376,NM_138957,NM_176795,NM_182734,NM_212535 GENE_SYMBOLS PRKCA,F2,PTGS1,MAPK3,TBXAS1,MAPK3,HRAS,TBXAS1,SYK,TBXAS1,TBXAS1,SYK,SYK,PTGS1,PTGS1,PTGS1,PTGS1,PTGS1,F2R,ITGB1,PRKCA,PRKCB,MAPK1,MAPK3,MAP2K1,RAF1,SYK,F2RL3,HRAS,PLCB1,PLA2G4A,TBXAS1,ITGB1,PTGS1,ITGB1,MAPK1,HRAS,PLCB1,PRKCB FOUNDER_NAMES