The Src family kinases and protein kinase C synergize to mediate G q-dependent platelet activation

Binggang Xiang, Guoying Zhang, Lucia Stefanini, Wolfgang Bergmeier, T. Kent Gartner, Sidney W. Whiteheart, Zhenyu Li

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The Src family kinases (SFKs) play essential roles in collagen-and von Willebrand factor (VWF)-mediated platelet activation. However, the roles of SFKs in G protein-coupled receptor-mediated platelet activation and the molecular mechanisms whereby SFKs are activated by G protein-coupled receptor stimulation are not fully understood. Here we show that the thrombin receptor protease-activated receptor 4 agonist peptide AYPGKF elicited SFK phosphorylation in P2Y12 deficient platelets but stimulated minimal SFK phosphorylation in platelets lacking Gq. We have previously shown that thrombin-induced SFK phosphorylation was inhibited by the calcium chelator 5,5′-dimethyl-bis-(o-aminophenoxy)ethane-N,N,N′,N′- tetraacetic acid (dimethyl-BAPTA). The calcium ionophore A23187 induced SFK phosphorylation in both wild-type and Gq deficient platelets. Together, these results indicate that SFK phosphorylation in response to thrombin receptor stimulation is downstream from Gq/Ca2+ signaling. Moreover, A23187-induced thromboxane A2 synthesis, platelet aggregation, and secretion were inhibited by preincubation of platelets with a selective SFK inhibitor, PP2. AYPGKF-induced thromboxane A2 production in wild-type and P2Y12 deficient platelets was abolished by PP2, and AYPGKF-mediated P-selectin expression, integrin α IIbβ3 activation, and aggregation of P2Y12 deficient platelets were partially inhibited by the PKC inhibitor Ro-31-8220, PP2, dimethyl-BAPTA, or LY294002, but were abolished by Ro-31-8220 plus PP2, dimethyl-BAPTA, or LY294002. These data indicate that Ca2+/SFKs/PI3K and PKC represent two alternative signaling pathways mediating G q-dependent platelet activation.

Original languageEnglish
Pages (from-to)41277-41287
Number of pages11
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Nov 30 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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