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Journal article
Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis
Angiogenesis (London), v 18(4), pp 449-462
01 Oct 2015
PMID: 26059764
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis
- Creators
- Srimathi Srinivasan - Boston UniversityVipul Chitalia - Boston UniversityRosana D Meyer - Boston UniversityEdward Hartsough - Boston UniversityManisha Mehta - Boston University School of MedicineItrat Harrold - Boston UniversityNicole Anderson - Boston UniversityHui Feng - Boston University School of MedicineLois E H Smith - Harvard UniversityYan Jiang - Boston UniversityCatherine E Costello - Boston UniversityNader Rahimi - Boston Medical Center
- Publication Details
- Angiogenesis (London), v 18(4), pp 449-462
- Publisher
- Springer Nature
- Grant note
- P41 RR010888 / NCRR NIH HHS R01EY017955 / NEI NIH HHS R21 CA191970 / NCI NIH HHS P41RR010888 / NCRR NIH HHS GM104603 / NIGMS NIH HHS R01 EY017955 / NEI NIH HHS R21 CA193958 / NCI NIH HHS K08 DK080946 / NIDDK NIH HHS HHSN268201000031C / NHLBI NIH HHS N01HV28178 / NHLBI NIH HHS R01 CA175382 / NCI NIH HHS DK080946 / NIDDK NIH HHS S10 RR020946 / NCRR NIH HHS P41 GM104603 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000362683200005
- Scopus ID
- 2-s2.0-84943361459
- Other Identifier
- 991020531820304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Peripheral Vascular Disease