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

University of Texas Health Science Center at Tyler, Tyler, Texas, United States
Journal of Pharmacological Sciences (Impact Factor: 2.11). 11/2007; 105(2):168-76. DOI: 10.1254/jphs.FP0070858
Source: PubMed

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) alpha-dependent. Importantly, knock-down of either PKD2 or PKCalpha 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 PKCalpha-dependent PKD2 activation could be an important mechanism in the early onset of AII-initiated endothelial adhesiveness.

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