Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation

Xiaona Ge, Brad Low, Mei Liang, Jian Fu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Angiotensin II (AII) has been reported to induce leukocyte adhesion to endothelium through up-regulation of P-selectin surface expression. However, the underlying molecular and cellular mechanisms remain unknown. P-selectin is stored in Weibel-Palade bodies (WPBs), large secretory granules, in endothelial cells. In this study, we examined the role of protein kinase D (PKD), a newly identified regulator of protein transport, in AII-induced WPB exocytosis and the resultant P-selectin surface expression. We demonstrated that PKD2 was rapidly activated by AII in endothelial cells through phosphorylation of the activation loop at Ser744/748. AII-induced PKD2 activation correlated with increased P-selectin surface expression. Furthermore, AII-regulated PKD2 activation is protein kinase C (PKC) α-dependent. Importantly, knock-down of either PKD2 or PKCα expression inhibited AII-mediated P-selectin surface expression and monocyte adhesion. Our findings provide the first evidence that stimulation of P-selectin surface expression via PKCα-dependent PKD2 activation could be an important mechanism in the early onset of AII-initiated endothelial adhesiveness.

Original languageEnglish
Pages (from-to)168-176
Number of pages9
JournalJournal of Pharmacological Sciences
Volume105
Issue number2
DOIs
StatePublished - 2007

Keywords

  • Angiotensin
  • Endothelial cell
  • Exocytosis
  • P-selectin
  • Protein kinase D (PKD)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint

Dive into the research topics of 'Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation'. Together they form a unique fingerprint.

Cite this