Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation.
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.
Ge
Xiaona
X
Center for Biomedical Research, University of Texas Health Center at Tyler, Tyler, Texas 75708, USA.
Low
Brad
B
Liang
Mei
M
Fu
Jian
J
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D015870:Gene Expression; D006041:Goats; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D020302:Weibel-Palade Bodies / Q000378:metabolism
D019007:P-Selectin; D000091283:Protein Kinase D2; D000804:Angiotensin II; D011494:Protein Kinases; D051571:Protein Kinase C-alpha