Suzuma, K.Takahara, N.Suzuma, I.Isshiki, K.Ueki, K.Leitges, M.Aiello, LloydKing, George2016-10-252002Suzuma, K., N. Takahara, I. Suzuma, K. Isshiki, K. Ueki, M. Leitges, L. P. Aiello, and G. L. King. 2002. Characterization of Protein Kinase C   Isoform’s Action on Retinoblastoma Protein Phosphorylation, Vascular Endothelial Growth Factor-Induced Endothelial Cell Proliferation, and Retinal Neovascularization. Proceedings of the National Academy of Sciences 99, no. 2: 721–726. doi:10.1073/pnas.022644499.0027-8424http://nrs.harvard.edu/urn-3:HUL.InstRepos:29074746Retinal 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 PKCβ2 isoform and a significant decrease in retinal neovascularization in PKCβ 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 PKCβ1 or β2 isoforms and inhibited significantly by the overexpression of a dominant-negative PKCβ2 isoform but not by the expression of PKC α, δ, and ζ isoforms. Association of PKCβ2 isoform with retinoblastoma protein was discovered in retinal endothelial cells, and PKCβ2 isoform increased retinoblastoma phosphorylation under basal and VEGF-stimulated conditions. The potential functional consequences of PKCβ-induced retinoblastoma phosphorylation could include enhanced E2 promoter binding factor transcriptional activity and increased VEGF-induced endothelial cell proliferation.en-USJournal Article2016-10-2510.1073/pnas.022644499