Journal
EMBO REPORTS
Volume 20, Issue 11, Pages -Publisher
WILEY
DOI: 10.15252/embr.201947845
Keywords
angiogenesis; GRB2; Nck; PI3Kp85; proliferation
Categories
Funding
- Swedish Research Council [2015-02375]
- Swedish Cancer Foundation [CAN2016/578]
- Knut and Alice Wallenberg Foundation [KAW 2015.0030]
- LCW Wallenberg Scholar grant [2015.0275]
- Swedish Research Council [2015-02375] Funding Source: Swedish Research Council
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available