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SALM4 regulates angiogenic functions in endothelial cells through VEGFR2 phosphorylation at Tyr1175

Published on Jun 6, 2019in The FASEB Journal5.39
· DOI :10.1096/fj.201802516RR
Dong-Young Kim5
Estimated H-index: 5
(Yonsei University),
Jeong Ae Park6
Estimated H-index: 6
(Yonsei University)
+ 6 AuthorsYoung-Guen Kwon46
Estimated H-index: 46
(Yonsei University)
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Abstract
Angiogenesis depends on VEGF-mediated signaling. However, the regulatory mechanisms and functions of individual VEGF receptor 2 (VEGFR2) phosphorylation sites remain unclear. Here, we report that synaptic adhesion-like molecule 4 (SALM4) regulates a specific VEGFR2 phosphorylation site. SALM4 silencing in HUVECs and Salm4 knockout (KO) in lung endothelial cells (ECs) of Salm4−/− mice suppressed phosphorylation of VEGFR2 tyrosine (Y) 1175 (Y1173 in mice) and downstream signaling upon VEGF-A stimulation. However, VEGFR2 phosphorylation at Y951 (Y949 in mice) and Y1214 (Y1212 in mice) remained unchanged. Knockdown and KO of SALM4 inhibited VEGF-A–induced angiogenic functions of ECs. SALM4 depletion reduced endothelial leakage, sprouting, and migratory activities. Furthermore, in an ischemia and reperfusion (I/R) model, brain injury was attenuated in Salm4−/− mice compared with wild-type (WT) mice. In brain lysates after I/R, VEGFR2 phosphorylation at Y949, Y1173, and Y1212 were induced in WT brains, but only...
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#1Ran Ao (PRC: China Medical University (PRC))H-Index: 3
#2Lin Guan (PRC: China Medical University (PRC))H-Index: 3
Last.Jia-Ni Wang (PRC: China Medical University (PRC))H-Index: 2
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#1Xiaoyan Jiang (Fudan University)H-Index: 10
#2Anuska V. Andjelkovic (UM: University of Michigan)H-Index: 28
Last.Yejie Shi (University of Pittsburgh)H-Index: 21
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#1Ikue Tai-Nagara (Keio: Keio University)H-Index: 4
#2Yusuke Yoshikawa (Keio: Keio University)H-Index: 3
Last.Bin Zhou (Yeshiva University)H-Index: 49
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