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

FEBS Lett. 2013 Jun 5;587(11):1624-9. doi: 10.1016/j.febslet.2013.04.015. Epub 2013 Apr 26.

Abstract

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-β (TGF-β) signaling. However, the mechanism underlying the regulation of TGF-β signaling is unclear. We show here that Dlg5 interacts and colocalizes with both TGF-β type I (TβRI) and type II (TβRII) receptors at the plasma membrane. TβRI activation is not required for this interaction. Furthermore, the overexpression of Dlg5 enhances the degradation of TβRI. Proteasome inhibitors inhibited this enhanced degradation. These results suggest that Dlg5 interacts with TβRs and promotes their degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Membrane / metabolism
  • HEK293 Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Proteolysis*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology
  • Tumor Suppressor Proteins / metabolism*

Substances

  • DLG5 protein, human
  • Membrane Proteins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II