TGF‐β1 induces rearrangement of FLK‐1–VE‐cadherin–β‐catenin complex at the adherens junction through VEGF‐mediated signaling

Abstract

VEGF and TGF-β1 induce angiogenesis but have opposing effects on vascular endothelial cells: VEGF promotes survival; TGF-β1 induces apoptosis. We have previously shown that TGF-β1 induces endothelial cell apoptosis via up-regulation of VEGF expression and activation of signaling through VEGF receptor-2 (flk-1). In context with TGF-β1, VEGF signaling is transiently converted from a survival into an apoptotic one. VEGF promotes cell survival in part via activation of PI3K/ Akt by a mechanism dependent on the formation of a multi-protein complex that includes flk-1 and the adherens junction proteins VE-cadherin and β-catenin. Here we report that TGF-β1 induces rearrangement of the adherens junction complex by separating flk-1 from VE-cadherin and increasing β-catenin association with both flk-1 and VE-cadherin. This rearrangement is caused neither by changes in adherens junction mRNA or protein expression nor by post-translational modification, and requires VEGF signaling through flk-1. These results show that the adherens junction is an important regulatory component of TGF-β1-VEGF interaction in endothelial cells.

Key Biomarkers