VEGF-induced activation of phosphoinositide 3-kinase is dependent on focaladhesion kinase

Citation
Jh. Qi et L. Claesson-welsh, VEGF-induced activation of phosphoinositide 3-kinase is dependent on focaladhesion kinase, EXP CELL RE, 263(1), 2001, pp. 173-182
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
0014-4827 → ACNP
Volume
263
Issue
1
Year of publication
2001
Pages
173 - 182
Database
ISI
SICI code
0014-4827(20010201)263:1<173:VAOP3I>2.0.ZU;2-T
Abstract
Vascular endothelial growth factor (VEGF)-A stimulates formation of new blo od vessels (angiogenesis). This process includes migration of endothelial c ells from the preexisting vessel toward the source of the growth factor. We show that VEGF-A-induced migration of porcine aortic endothelial cells exp ressing VEGF receptor-2 (VEGFR-2) is dependent on activation of phosphoinos itide 3-kinase (PI3-kinase). There is no direct interaction between VEGF re ceptor-2 and PI3-kinase; instead PI3-kinase is activated downstream of foca l adhesion kinase (FAK) in VEGF-A-stimulated cells. Thus, VEGF-A stimulatio n leads to complex formation between FAK and PI3-kinase and overexpression of dominant-negative FAK decreases VEGF-A-induced PI3-kinase activation. FA K activation by VEGF-A increases with increasing concentration of growth fa ctor, without apparent collapse of the cytoskeleton, in contrast to the eff ect of platelet-derived growth factor. FAK activation is mediated via the C -terminal tail of VEGFR-2 and loss of VEGF-A-induced FAK activation in cell s expressing mutant VEGFR-2 correlates with loss of migration capacity. The se data show that VEGF-A-induced FAK and PI3-kinase activation are required for migration of cells expressing VEGFR-2, via a pathway independent of di rect interaction with the receptor. (C) 2001 Academic Press.