Essential role of protein kinase Cδ in platelet signaling, αIIbβ3 activation, and thromboxane A 2 release

Daniel Yacoub, Jean François Théorêt, Louis Villeneuve, Haissam Abou-Saleh, Walid Mourad, Bruce G. Allen, Yahye Merhi

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    Abstract

    The protein kinase C (PKC) family is an essential signaling mediator in platelet activation and aggregation. However, the relative importance of the major platelet PKC isoforms and their downstream effectors in platelet signaling and function remain unclear. Using isolated human platelets, we report that PKCδ, but not PKCα or PKCβ, is required for collagen-induced phospholipase C-dependent signaling, activation of αIIbβ 3, and platelet aggregation. Analysis of PKCδ phosphorylation and translocation to the membrane following activation by both collagen and thrombin indicates that it is positively regulated by α IIbβ3 outside-in signaling. Moreover, PKCδ triggers activation of the mitogen-activated protein kinase-kinase (MEK)/extracellular-signal regulated kinase (ERK) and the p38 MAPK signaling. This leads to the subsequent release of thromboxane A2, which is essential for collagen-induced but not thrombin-induced platelet activation and aggregation. This study adds new insight to the role of PKCs in platelet function, where PKCδ signaling, via the MEK/ERK and p38 MAPK pathways, is required for the secretion of thromboxane A2.

    Original languageEnglish
    Pages (from-to)30024-30035
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume281
    Issue number40
    DOIs
    Publication statusPublished - 6 Oct 2006

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Yacoub, D., Théorêt, J. F., Villeneuve, L., Abou-Saleh, H., Mourad, W., Allen, B. G., & Merhi, Y. (2006). Essential role of protein kinase Cδ in platelet signaling, αIIbβ3 activation, and thromboxane A 2 release. Journal of Biological Chemistry, 281(40), 30024-30035. https://doi.org/10.1074/jbc.M604504200