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PMID:17951978

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Citation

Ge, X, Low, B, Liang, M and Fu, J (2007) Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation. J. Pharmacol. Sci. 105:168-76

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.

Links

PubMed

Keywords

Angiotensin II/pharmacology; Animals; Cell Adhesion; Cells, Cultured; Endothelium, Vascular/metabolism; Exocytosis/physiology; Gene Expression; Goats; Humans; Immunoblotting; Mice; P-Selectin/metabolism; Phosphorylation; Protein Kinase C-alpha/metabolism; Protein Kinases/metabolism; Rabbits; Weibel-Palade Bodies/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:KPCD2

involved_in

GO:0045785: positive regulation of cell adhesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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