Protein kinase cδ differentially regulates platelet functional responses

Ramya Chari, Todd Getz, Bela Nagy, Kamala Bhavaraju, Yingying Mao, Yamini Saraswathy Bynagari, Swaminathan Murugappan, Keiko Nakayama, Satya P. Kunapuli

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

OBJECTIVE-: Protein Kinase C delta (PKCδ) is expressed in platelets and activated downstream of protease-activated receptors (PAR)s and glycoprotein VI (GPVI) receptors. The purpose of this study was to investigate the role of PKCδ in platelets. METHODS AND RESULTS-: We evaluated the role of PKCδ in platelets using two approaches-pharmacological and molecular genetic approach. In human platelets pretreated with isoform selective antagonistic RACK peptide (δ V1-1)TAT, and in the murine platelets lacking PKCδ, PAR4-mediated dense granule secretion was inhibited, whereas GPVI-mediated dense granule secretion was potentiated. These effects were statistically significant in the absence and presence of thromboxane A2 (TXA2). Furthermore, TXA2 generation was differentially regulated by PKCδ. However, PKCδ had a small effect on platelet P-selectin expression. Calcium- and PKC-dependent pathways independently activate fibrinogen receptor in platelets. When calcium pathways are blocked by dimethyl-BAPTA, AYPGKF-induced aggregation in PKCδ null mouse platelets and in human platelets pretreated with (δ V1-1)TAT, was inhibited. In a FeCl3-induced injury in vivo thrombosis model, PKCδ mice occluded similar to their wild-type littermates. CONCLUSIONS-: Hence, we conclude that PKCδ differentially regulates platelet functional responses such as dense granule secretion and TXA2 generation downstream of PARs and GPVI receptors, but PKCδ deficiency does not affect the thrombus formation in vivo.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number5
DOIs
Publication statusPublished - 2009 May

Keywords

  • Fibrinogen
  • Platelets
  • Protein kinase C
  • Secretion
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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