c-Cbl-Dependent Monoubiquitination and Lysosomal Degradation of gp130

• DOI: 10.1128/mcb.01784-07
• Publication Date: 2008-06-03T00:57:20Z
• Authors: Yoshinori Tanaka; Nobuyuki Tanaka; Yasushi Saeki; Keiji Tanaka; Masaaki Murakami; Toshio Hirano; Naoto Ishii; Kazuo Sugamura
• Keywords: Glycoprotein 130

Interleukin 6 (IL-6), a pleiotropic cytokine, functions in cells through its interaction with receptor complex, which consists of two ligand-binding alpha subunits and signal-transducing known as gp130. There is wealth studies on signals mediated by gp130, but downregulation less well understood. Here we found that IL-6 stimulation induced lysosome-dependent degradation correlated an increase the K63-linked polyubiquitination The stimulation-dependent ubiquitination gp130 was c-Cbl, E3 ligase, recruited to tyrosine-phosphorylated SHP2-dependent manner. We also rapid translocation from cell surface endosomal compartments. Furthermore, vesicular sorting molecule Hrs contributed lysosomal directly recognizing ubiquitinated form. Deficiency either or c-Cbl suppressed degradation, leads prolonged amplified signal. Thus, our present report provides first evidence for involvement c-Cbl/SHP2 complex upon stimulation. critical cessation IL-6-mediated signaling.