PKCθ is required for hemostasis and positive regulation of thrombin-induced platelet aggregation and α-granule secretion

Sagit Cohen, Alex Braiman, George Shubinsky, Ariel Ohayon, Amnon Altman, Noah Isakov

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Platelet activation due to vascular injury is essential for hemostatic plug formation, and is mediated by agonists, such as thrombin, which trigger distinct receptor-coupled signaling pathways. Thrombin is a coagulation protease, which activates G protein-coupled protease-activated receptors (PARs) on the surface of platelets. We found that C57BL/6J and BALB/C mice that are deficient in protein kinase C θ (PKCθ), exhibit an impaired hemostasis, and prolonged bleeding following vascular injury. In addition, murine platelets deficient in PKCθ displayed an impaired thrombin-induced platelet activation and aggregation response. Lack of PKCθ also resulted in impaired α-granule secretion, as demonstrated by the low surface expression of CD62P, in thrombin-stimulated platelets. Since PAR4 is the only mouse PAR receptor that delivers thrombin-induced activation signals in platelets, our results suggest that PKCθ is a critical effector molecule in the PAR4-linked signaling pathways and in the regulation of normal hemostasis in mice.

Original languageEnglish
Pages (from-to)22-27
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume385
Issue number1
DOIs
StatePublished - 17 Jul 2009

Keywords

  • Aggregation
  • CD62P
  • Hemostasis
  • P-selectin
  • PAR4
  • Platelets
  • Protein kinase C θ
  • Thrombin
  • Thrombus formation
  • α-Granules

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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