Purchase this article with an account.
Manisha N. Mehta, Srimathi Srinivasan, Rosana D. Meyer, Ricardo Lugo, Vipul Chitalia, Nader Rahimi; PDCL3 Regulates Endothelial Cell Proliferation And Angiogenesis Through The Generation Of Functional VEGFR-2. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3005.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Angiogenesis, a hallmark step in ocular neovascularization, is primarily driven by the function of VEGF on its receptor, VEGFR-2. Central to the initiation of angiogenesis by VEGF, the abundance of VEGFR-2 on the surface of endothelial cells is essential for VEGF to recognize and activate VEGFR-2. We have identified PDCL3 (phosducin like 3) as a novel protein involved in the stabilization of VEGFR-2 by serving as a VEGFR-2 co-chaperone protein.
Various molecular and cell biology methods including Western blotting, site direct mutagenesis, endothelial cell culture systems, knock-down experiments with siRNA, invitro-angiogenesis assays and immunohistochemical studies on mouse eyes exposed to hypoxia were used to study the role of PDCL3 in regulation of VGFR2 in endometrial cells.
PDCL3 expression is upregulated by hypoxia in endothelial cells and its expression is responsible for hypoxia-induced expression of VEGFR-2. PDCL3 co-localizes with VEGFR-2 in cells and recognizes the JM domain of VEGFR-2. Over-expression of PDCL3 increases, whereas depleting its expression by siRNA in endothelial cells reduces the abundance of VEGFR-2 protein. Upregulation of PDCL3 markedly increases ligand-mediated activation of VEGFR-2.
Our studies provide experimental evidence for the role of PDCL3 in governing the angiogenic pathway by controlling VEGFR-2 destruction. PDCL3 elicits its activity by rendering VEGFR-2 to a more stable protein by preventing its ubiquitylation and degradation. PDCL3 activity is required for endothelial cell proliferation and tube formation of endothelial cells and angiogenesis.
This PDF is available to Subscribers Only