Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
FEBS Lett. 2013 Jun 5;587(11):1624-9. doi: 10.1016/j.febslet.2013.04.015. Epub 2013 Apr 26.
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.
Discs large 同源物 5 (Dlg5) 是膜相关鸟苷酸激酶衔接蛋白家族的成员，通过转化生长因子-β (TGF-β) 信号通路参与上皮间质转化。然而，TGF-β 信号通路的调节机制尚不清楚。本研究表明 Dlg5 与 TGF-β Ⅰ型 (TβRI) 和Ⅱ型 (TβRII) 受体在质膜上相互作用并共定位。TβRI 的激活不是这种相互作用所必需的。此外，Dlg5 的过表达增强了 TβRI 的降解。蛋白酶体抑制剂抑制了这种增强的降解。这些结果表明 Dlg5 与 TβRs 相互作用并促进其降解。
