Identification of protein kinase D2 as a pivotal regulator of endothelial cell proliferation, migration, and angiogenesis.
Angiogenesis, the formation of new blood vessels, plays a crucial role in normal physiological processes and in various pathological conditions. In the present study, we have investigated the physiological function of a newly described serine/threonine protein kinase D2 (PKD2) in aspects of endothelial cell biology involved in angiogenesis. We found that PKD2 was expressed in primary human endothelial cells from different tissues and was a critical PKD isoform mediating the phosphorylation of PKD substrates in endothelial cells. By using small interference RNAs that target different PKD2 regions, we found that silencing PKD2, but not PKD1 isoform, markedly inhibited the proliferation, migration, and in vitro angiogenesis of endothelial cells cultured in EGM-2 complete medium. We further showed that PKD2, but not PKD1, was required for the expression of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 that are two key growth factor receptors involved in angiogenesis. These findings indicate that PKD2 plays a pivotal role in endothelial cell proliferation and migration necessary for angiogenesis at least in part through modulation of the expression of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1.
Hao
Qin
Q
Department of Biochemistry, The University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
Wang
Linping
L
Zhao
Z Joe
ZJ
Tang
Hua
H
D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D007527:Isoenzymes; D000091283:Protein Kinase D2; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D013755:Tetradecanoylphorbol Acetate