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Axl is essential for VEGF-A-dependent activation of PI3K/Akt.

The EMBO journal (2012-02-14)
Guo-Xiang Ruan, Andrius Kazlauskas
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Phosphotyrosine Antibody, clone 4G10®, clone 4G10®, Upstate®, from mouse
Sigma-Aldrich
In Vitro Vascular Permeability Assay (96-well), This In Vitro Vascular Permeability Assay kit employs a 96-well plate, and provides an efficient system for evaluating the effects of chemicals & drug compounds on endothelial cell adsorption, transport & permeability.