Authored: Ray, K, 2010-12-13 SHP2 binds CBL in response to IL-6 stimulation in 293T cells and contributes to the ubiquitination of gp130 (Tanaka et al. 2008).<br> 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. Edited: Jupe, S, 2010-12-10 Reviewed: Rose-John, S, 2011-02-11

http://purl.obolibrary.org/obo/HINO_0006392

Authored: Ray, K, 2010-12-13

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.

Edited: Jupe, S, 2010-12-10

Reviewed: Rose-John, S, 2011-02-11

Reactome, http://www.reactome.org

Pubmed18519587

http://purl.obolibrary.org/obo/UniProt_P22681

http://purl.obolibrary.org/obo/HINO_0026148

http://purl.obolibrary.org/obo/HINO_0026150

SHP2 binds c-Cbl upon IL-6 stimulation

HINO:0006392

SHP2 binds c-Cbl upon IL-6 stimulation

ReactomeREACT_27220

Reactome Database ID Release 431112690

http://purl.obolibrary.org/obo/INO_0000040