Characterization of protein kinase C β isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization

被引:139
作者
Suzuma, K
Takahara, N
Suzuma, I
Isshiki, K
Ueki, K
Leitges, M
Aiello, LP
King, GL [1 ]
机构
[1] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA
[2] Max Planck Expt Endokrinol, D-30625 Hannover, Germany
关键词
D O I
10.1073/pnas.022644499
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Retinal neovascularization is a major cause of blindness and requires the activities of several signaling pathways and multiple cytokines. Activation of protein kinase C (PKC) enhances the angiogenic process and is involved in the signaling of vascular endothelial growth factor (VEGF). We have demonstrated a dramatic increase in the angiogenic response to oxygen-induced retinal ischemia in transgenic mice overexpressing PKCbeta2 isoform and a significant decrease in retinal neovascularization in PKCbeta isoform null mice. The mitogenic action of VEGF, a potent hypoxia-induced angiogenic factor, was increased by 2-fold in retinal endothelial cells by the overexpression of PKCbeta1 or beta2 isoforms and inhibited significantly by the overexpression of a dominant-negative PKCbeta2 isoform but not by the expression of PKC alpha, delta, and isoforms. Association of PKCbeta2 isoform with retinoblastoma protein was discovered in retinal endothelial cells, and PKCbeta2 isoform increased retinoblastoma phosphorylation under basal and VEGF-stimulated conditions. The potential functional consequences of PKCbeta-induced retinoblastoma phosphorylation could include enhanced E2 promoter binding factor transcriptional activity and increased VEGF-induced endothelial cell proliferation.
引用
收藏
页码:721 / 726
页数:6
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