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

Research output: Contribution to journalArticle

56 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Thromboxanes
Platelets
varespladib methyl
Protein Kinase C
Blood Platelets
Chemical activation
Mitogen-Activated Protein Kinase Kinases
Platelet Aggregation
Thromboxane A2
Collagen
Agglomeration
Extracellular Signal-Regulated MAP Kinases
Platelet Activation
p38 Mitogen-Activated Protein Kinases
Thrombin
Phosphorylation
Type C Phospholipases
Protein Isoforms
Membranes

ASJC Scopus subject areas

  • Biochemistry

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

Essential role of protein kinase Cδ in platelet signaling, αIIbβ3 activation, and thromboxane A 2 release. / Yacoub, Daniel; Théorêt, Jean François; Villeneuve, Louis; Abou-Saleh, Haissam; Mourad, Walid; Allen, Bruce G.; Merhi, Yahye.

In: Journal of Biological Chemistry, Vol. 281, No. 40, 06.10.2006, p. 30024-30035.

Research output: Contribution to journalArticle

Yacoub, D, Théorêt, JF, Villeneuve, L, Abou-Saleh, H, Mourad, W, Allen, BG & Merhi, Y 2006, 'Essential role of protein kinase Cδ in platelet signaling, αIIbβ3 activation, and thromboxane A 2 release', Journal of Biological Chemistry, vol. 281, no. 40, pp. 30024-30035. https://doi.org/10.1074/jbc.M604504200
Yacoub, Daniel ; Théorêt, Jean François ; Villeneuve, Louis ; Abou-Saleh, Haissam ; Mourad, Walid ; Allen, Bruce G. ; Merhi, Yahye. / Essential role of protein kinase Cδ in platelet signaling, αIIbβ3 activation, and thromboxane A 2 release. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 40. pp. 30024-30035.
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