Reactome: A Curated Pathway Database

SHP2 binds c-Cbl upon IL-6 stimulation (R-HSA-1112690) [Homo sapiens]


SHP2 binds CBL in response to IL-6 stimulation in 293T cells and contributes to the ubiquitination of gp130 (Tanaka et al. 2008).
IL-6 stimulation induced lysosome-dependent degradation of gp130, which correlated with an increase in its K63-linked polyubiquitination. This stimulation-dependent ubiquitination was mediated by CBL, an E3 ligase, which was recruited to gp130 in a tyrosine-phosphorylated SHP2-dependent manner. IL-6 induced a rapid translocation of gp130 from the cell surface to endosomal compartments. The vesicular sorting molecule Hrs contributed to the lysosomal degradation of gp130 by directly recognizing its ubiquitinated form. Deficiency of either Hrs or CBL suppressed gp130 degradation, leading to a prolonged and amplified IL-6 signal.

Additional Information
Compartment plasma membrane , cytosol
Literature References
pubMedId Title Journal Year
18519587 c-Cbl-dependent monoubiquitination and lysosomal degradation of gp130 Mol Cell Biol 2008