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.
VE-cadherin is a critical endothelial regulator of TGF-beta signalling / N. Rudini, A. Felici, C. Giampietro, M.G. Lampugnani, M. Corada, K. Swirsding, M. Garrè, S. Liebner, M. Letarte, P. ten Dijke, E. Dejana. - In: EMBO JOURNAL. - ISSN 0261-4189. - 27:7(2008), pp. 993-1004.
VE-cadherin is a critical endothelial regulator of TGF-beta signalling
N. Rudini;C. Giampietro;E. Dejana
2008
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-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.File | Dimensione | Formato | |
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