DOI: 10.1073/pnas.022644499. Characterization of protein kinase C β isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization

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

10.1073/pnas.022644499

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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 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.

Bibliography

Suzuma, K., Takahara, N., Suzuma, I., Isshiki, K., Ueki, K., Leitges, M., Aiello, L. P., & King, G. L. (2002). Characterization of protein kinase C Î² isoformâs action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization. Proceedings of the National Academy of Sciences, 99(2), 721â726.

Authors 8

Kiyoshi Suzuma (first)
Noriko Takahara (additional)
Izumi Suzuma (additional)
Keiji Isshiki (additional)
Kohjiro Ueki (additional)
Michael Leitges (additional)
Lloyd Paul Aiello (additional)
George L. King (additional)

References 32 Referenced 140

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:36 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 9:02 a.m.)
Indexed	1 week, 3 days ago (Aug. 26, 2025, 2:29 a.m.)
Issued	23 years, 7 months ago (Jan. 22, 2002)
Published	23 years, 7 months ago (Jan. 22, 2002)
Published Online	23 years, 7 months ago (Jan. 22, 2002)
Published Print	23 years, 7 months ago (Jan. 22, 2002)

Funders 0

None

BibTeX

@article{Suzuma_2002, title={Characterization of protein kinase C β isoform’s action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.022644499}, DOI={10.1073/pnas.022644499}, number={2}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Suzuma, Kiyoshi and Takahara, Noriko and Suzuma, Izumi and Isshiki, Keiji and Ueki, Kohjiro and Leitges, Michael and Aiello, Lloyd Paul and King, George L.}, year={2002}, month=jan, pages={721–726} }

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