| First Author | Ruan GX | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 7 | Pages | 1692-703 |
| PubMed ID | 22327215 | Mgi Jnum | J:182517 |
| Mgi Id | MGI:5315793 | Doi | 10.1038/emboj.2012.21 |
| Citation | Ruan GX, et al. (2012) Axl is essential for VEGF-A-dependent activation of PI3K/Akt. EMBO J 31(7):1692-703 |
| abstractText | 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. |
