Angiotensin II Directly Triggers Endothelial Exocytosis via Protein Kinase C-Dependent Protein Kinase D2 Activation

[摘要] References(52)Cited-By(11)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.

[学科分类] 药学

[关键词] angiotensin;P-selectin;exocytosis;endothelial cell;protein kinase D (PKD)