@article {560191,
	title = {Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis.},
	journal = {Angiogenesis},
	volume = {18},
	number = {4},
	year = {2015},
	month = {2015 Oct},
	pages = {449-62},
	abstract = {Expression and activation of vascular endothelial growth factor receptor 2 (VEGFR-2) by VEGF ligands are the main events in the stimulation of pathological angiogenesis. VEGFR-2 expression is generally low in the healthy adult blood vessels, but its expression is markedly increased in the pathological angiogenesis. In this report, we demonstrate that phosducin-like 3 (PDCL3), a recently identified chaperone protein involved in the regulation of VEGFR-2 expression, is required for angiogenesis in zebrafish and mouse. PDCL3 undergoes N-terminal methionine acetylation, and this modification affects PDCL3 expression and its interaction with VEGFR-2. Expression of PDCL3 is regulated by hypoxia, the known stimulator of angiogenesis. The mutant PDCL3 that is unable to undergo N-terminal methionine acetylation was refractory to the effect of hypoxia. The siRNA-mediated silencing of PDCL3 decreased VEGFR-2 expression resulting in a decrease in VEGF-induced VEGFR-2 phosphorylation, whereas PDCL3 over-expression increased VEGFR-2 protein. Furthermore, we show that PDCL3 protects VEGFR-2 from misfolding and aggregation. The data provide new insights for the chaperone function of PDCL3 in angiogenesis and the roles of hypoxia and N-terminal methionine acetylation in PDCL3 expression and its effect on VEGFR-2.},
	issn = {1573-7209},
	doi = {10.1007/s10456-015-9468-3},
	author = {Srinivasan, Srimathi and Chitalia, Vipul and Meyer, Rosana D and Hartsough, Edward and Mehta, Manisha and Harrold, Itrat and Anderson, Nicole and Feng, Hui and Smith, Lois E H and Jiang, Yan and Costello, Catherine E and Rahimi, Nader}
}
