Dlg5 interacts with the TGF-β receptor and promotes its degradation

Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase adaptor family of proteins and is involved in epithelial-to-mesenchymal transition via transforming growth factor-beta (TGF-beta) signaling. However, the mechanism underlying the regulation of TGF-beta signaling is unclear. We show here that Dlg5 interacts and colocalizes with both TGF-beta type I (T beta RI) and type II (T beta RII) receptors at the plasma membrane. T beta RI activation is not required for this interaction. Furthermore, the overexpression of Dlg5 enhances the degradation of T beta RI. Proteasome inhibitors inhibited this enhanced degradation. These results suggest that Dlg5 interacts with T beta Rs and promotes their degradation. Structured summary of protein interactions: DLG5 physically interacts with T beta RII and T beta RI by anti tag coimmunoprecipitation (View interaction) DLG5 physically interacts with T beta RII by anti tag coimmunoprecipitation (View interaction) T beta RI physically interacts with DLG5 by anti bait coimmunoprecipitation (View interaction) DLG5, T beta RI and T beta RII colocalize by fluorescence microscopy (View interaction) DLG5 physically interacts with T beta RI by anti tag coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.