The docking protein FRS2α is a critical regulator of VEGF receptors signaling.
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.
Yale Cardiovascular Research Center, Department of Internal Medicine, and Departments of Surgery, Pharmacology, and Cell Biology, Yale University School of Medicine, New Haven, CT 06520.
Pei-Yu
PY
Chen
Lingfeng
L
Qin
Zhen W
ZW
Zhuang
George
G
Tellides
Irit
I
Lax
Joseph
J
Schlessinger
Michael
M
Simons
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells; D020869:Gene Expression Profiling; D005822:Genetic Vectors; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017078:Laser-Doppler Flowmetry; D016086:Lentivirus; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D055114:X-Ray Microtomography
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C106534:FRS2 protein, human; D008565:Membrane Proteins; D040262:Receptors, Vascular Endothelial Growth Factor
FGF receptor; MAP kinase; phosphorylation; receptor kinase inhibition; signal transduction