Vascular endothelial growth factor stimulates dephosphorylation of the catenins p120 and p100 in endothelial cells

Abstract

Vascular endothelial growth factor (VEGF) is an endothelium-specific mitogen that induces angiogenesis and increases vascular permeability. These processes involve regulation of cell-cell adhesion, but molecular mechanisms have yet to be fully established. p120, also termed p120ctn, and its variant p100 are catenins which associate with cadherins and localize to adherens junctions. VEGF was reported to stimulate tyrosine phosphorylation of catenins in endothelial cells. In contrast, we have found that VEGF potently stimulated a rapid and dose-dependent decrease in serine/threonine phosphorylation of p120 and p100. VEGF acted via VEGF receptor 2 to achieve this effect which was independent of activation of the extracellular-signal-regulated kinase pathway. Histamine and activators of protein kinase C had a very similar effect to that of VEGF on phosphorylation of p120 and p100, suggesting that these diverse stimuli may converge on a common signalling element regulating p120/p100 serine/threonine phosphorylation. These data raise the possibility that the dephosphorylation of p120 and p100 triggered by VEGF may contribute to mechanisms regulating permeability and/or motility through modulation of cadherin adhesiveness.