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In the endothelium, VEGF mediates most of its angiogenic effects through VEGF receptor 2 (VEGFR2). To understand the role of EMCN, we examined the effect of EMCN depletion on VEGFR2 endocytosis and activation. Results showed that although VEGF stimulation promoted VEGFR2 internalization in control endothelial cells (ECs), loss of EMCN prevented VEGFR2 endocytosis. Cell surface analysis revealed a decrease in VEGFR2 following VEGF stimulation in control but not siRNA directed against EMCN\u2014transfected ECs. EMCN depletion resulted in heightened phosphorylation following VEGF stimulation with an increase in total VEGFR2 protein. These results indicate that EMCN modulates VEGFR2 endocytosis and activity and point to EMCN as a potential therapeutic target.\u2014LeBlanc, M. E., Saez\u2010Torres, K. L., Cano, I., Hu, Z., Saint\u2010Geniez, M., Ng, Y.\u2010S., D'Amore, P. A. Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity. FASEB J. 33, 9362\u20139373 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900011r","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T14:06:41Z","timestamp":1559138801000},"page":"9362-9373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity"],"prefix":"10.1096","volume":"33","author":[{"given":"Michelle E.","family":"Leblanc","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahira L.","family":"Saez\u2010Torres","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issahy","family":"Cano","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Hu","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Saint\u2010Geniez","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin\u2010Shan","family":"Ng","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"D'Amore","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Department of Ophthalmology Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Pathology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"XE01","article-title":"Tumour angiogenesis and angiogenic inhibitors: a review","volume":"9","author":"Yadav L.","year":"2015","journal-title":"J. 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