The role of protein kinase C in α-thrombin-mediated endothelial cell activation

J. E. Stasek, J. G.N. Garcia

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

Thrombin, the key regulatory protein of hemostasis, has been implicated in a variety of important endothelial cell processes closely linked to endothelial signal transduction mechanisms. An initial event, following receptor binding by catalytically active α-thrombin, appears to be the activation of a G-protein-coupled, PI-specific PLC, with resultant generation of IP3 and DAG, with increases in [Ca2+)(i), and activation and translocation of PKC (Fig. 9). PKC activation results in down-regulation of PLC, as demonstrated by inhibition of agonist-induced increases in [Ca2+](i), whereas PLA2 activity is up-regulated, with a resultant increase in endothelial PGI2 synthesis. Recently, we have demonstrated that activity of membrane-bound, endothelial PLD, is also up-regulated by PKC activation. In addition to its modulatory role in endothelial cell phospholipase activities, PKC activation appears to play a critical role in thrombin-mediated endothelial barrier dysfunction, likely via specific cytoskeletal protein phosphorylation. A temporal relationship between α-thrombin-mediated signal transduction and specific cellular responses, such as PGI2 synthesis and barrier dysfunction, can be established (Fig. 2). Further investigations are ongoing to identify more clearly the precise biochemical intermediates involved in the endothelial cell response to thrombin, as well as the role of differential phosphorylation by various protein kinase systems in thrombin-mediated signal transduction in vascular endothelium.

Original languageEnglish (US)
Pages (from-to)117-125
Number of pages9
JournalSeminars in Thrombosis and Hemostasis
Volume18
Issue number1
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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