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Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5514-9. doi: 10.1073/pnas.1404545111. Epub 2014 Apr 2.

The docking protein FRS2α is a critical regulator of VEGF receptors signaling.

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  • 1Yale Cardiovascular Research Center, Department of Internal Medicine, and Departments of Surgery, Pharmacology, and Cell Biology, Yale University School of Medicine, New Haven, CT 06520.


Vascular endothelial growth factors (VEGFs) signal via their cognate receptor tyrosine kinases designated VEGFR1-3. We report that the docking protein fibroblast growth factor receptor substrate 2 (FRS2α) plays a critical role in cell signaling via these receptors. In vitro FRS2α regulates VEGF-A and VEGF-C-dependent activation of extracellular signal-regulated receptor kinase signaling and blood and lymphatic endothelial cells migration and proliferation. In vivo endothelial-specific deletion of FRS2α results in the profound impairment of postnatal vascular development and adult angiogenesis, lymphangiogenesis, and arteriogenesis. We conclude that FRS2α is a previously unidentified component of VEGF receptors signaling.


FGF receptor; MAP kinase; phosphorylation; receptor kinase inhibition; signal transduction

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