TY - JOUR
T1 - Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation
AU - Ge, Xiaona
AU - Low, Brad
AU - Liang, Mei
AU - Fu, Jian
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Angiotensin
KW - Endothelial cell
KW - Exocytosis
KW - P-selectin
KW - Protein kinase D (PKD)
UR - http://www.scopus.com/inward/record.url?scp=36148990584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36148990584&partnerID=8YFLogxK
U2 - 10.1254/jphs.FP0070858
DO - 10.1254/jphs.FP0070858
M3 - Article
C2 - 17951978
AN - SCOPUS:36148990584
SN - 1347-8613
VL - 105
SP - 168
EP - 176
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 2
ER -