| First Author | Testini C | Year | 2019 |
| Journal | EMBO Rep | Volume | 20 |
| Issue | 11 | Pages | e47845 |
| PubMed ID | 31545012 | Mgi Jnum | J:286471 |
| Mgi Id | MGI:6390712 | Doi | 10.15252/embr.201947845 |
| Citation | Testini C, et al. (2019) Myc-dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor-2. EMBO Rep 20(11):e47845 |
| abstractText | Exaggerated signaling by vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR2, in pathologies results in poor vessel function. Still, pharmacological suppression of VEGFA/VEGFR2 may aggravate disease. Delineating VEGFR2 signaling in vivo provides strategies for suppression of specific VEGFR2-induced pathways. Three VEGFR2 tyrosine residues (Y949, Y1212, and Y1173) induce downstream signaling. Here, we show that knock-in of phenylalanine to create VEGFR2 Y1212F in C57Bl/6 and FVB mouse strains leads to loss of growth factor receptor-bound protein 2- and phosphoinositide 3'-kinase (PI3K)p85 signaling. C57Bl/6 Vegfr2(Y1212F/Y1212F) show reduced embryonic endothelial cell (EC) proliferation and partial lethality. FVB Vegfr2(Y1212F/Y1212F) show reduced postnatal EC proliferation. Reduced EC proliferation in Vegfr2(Y1212F/Y1212F) explants is rescued by c-Myc overexpression. We conclude that VEGFR2 Y1212 signaling induces activation of extracellular-signal-regulated kinase (ERK)1/2 and Akt pathways required for c-Myc-dependent gene regulation, endothelial proliferation, and vessel stability. |
