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-β (TGF-β) signalling in endothelial cells (ECs). TGF-β antiproliferative and antimigratory responses are increased in the presence of VE-cadherin. ECs lacking VE-cadherin are less responsive to TGF-β/ALK1- and TGF-β/ALK5-induced Smad phosphorylation and target gene transcription. VE-cadherin coimmunoprecipitates with all the components of the TGF-β receptor complex, TβRII, ALK1, ALK5 and endoglin. Clustered VE-cadherin recruits TβRII and may promote TGF-β signalling by enhancing TβRII/TβRI assembly into an active receptor complex. Taken together, our data indicate that VE-cadherin is a positive and EC-specific regulator of TGF-β signalling. This suggests that reduction or inactivation of VE-cadherin may contribute to progression of diseases where TGF-β signalling is impaired.
|Titolo:||VE-cadherin is a critical endothelial regulator of TGF-beta signalling|
|Parole Chiave:||Endothelial cells; Signal transduction; Smad; TGF-β; VE-cadherin|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||10.1038/emboj.2008.46|
|Appare nelle tipologie:||01 - Articolo su periodico|