| Literature DB >> 18337748 |
Noemi Rudini1, Angelina Felici, Costanza Giampietro, MariaGrazia Lampugnani, Monica Corada, Kendra Swirsding, Massimiliano Garrè, Stefan Liebner, Michelle Letarte, Peter ten Dijke, Elisabetta Dejana.
Abstract
VE-cadherin is an endothelial-specific transmembrane protein concentrated at cell-to-cell adherens junctions. Besides promoting cell adhesion and controlling vascular permeability, VE-cadherin transfers intracellular signals that contribute to vascular stabilization. However, the molecular mechanism by which VE-cadherin regulates vascular homoeostasis is still poorly understood. Here, we report that VE-cadherin expression and junctional clustering are required for optimal transforming growth factor-beta (TGF-beta) signalling in endothelial cells (ECs). TGF-beta antiproliferative and antimigratory responses are increased in the presence of VE-cadherin. ECs lacking VE-cadherin are less responsive to TGF-beta/ALK1- and TGF-beta/ALK5-induced Smad phosphorylation and target gene transcription. VE-cadherin coimmunoprecipitates with all the components of the TGF-beta receptor complex, TbetaRII, ALK1, ALK5 and endoglin. Clustered VE-cadherin recruits TbetaRII and may promote TGF-beta signalling by enhancing TbetaRII/TbetaRI assembly into an active receptor complex. Taken together, our data indicate that VE-cadherin is a positive and EC-specific regulator of TGF-beta signalling. This suggests that reduction or inactivation of VE-cadherin may contribute to progression of diseases where TGF-beta signalling is impaired.Entities:
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Year: 2008 PMID： 18337748 PMCID： PMC2323269 DOI： 10.1038/emboj.2008.46
Source DB: PubMed Journal: EMBO J ISSN： 0261-4189 Impact factor: 11.598