Journal
EMBO JOURNAL
Volume 31, Issue 7, Pages 1692-1703Publisher
WILEY
DOI: 10.1038/emboj.2012.21
Keywords
angiogenesis; Axl; PI3K; VEGF-A; VEGFR-2
Categories
Funding
- Juvenile Diabetes Research Foundation (JDRF) [12008905, 32009560, 102011367]
- NIH [EY016385]
Ask authors/readers for more resources
Herein, we report that vascular endothelial growth factor A (VEGF-A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF-A-dependent activation of VEGF receptor-2 (VEGFR-2), and subsequent TSAd-mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand-independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF-A-mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF-A- but not bFGF-dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF-A-induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF-A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes. The EMBO Journal (2012) 31, 1692-1703. doi: 10.1038/emboj.2012.21; Published online 10 February 2012
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