Authored: Ray, KP, 2010-05-17 Cbl is constitutively associated with Grb2 in resting hematopoietic cells (Anderson et al. 1997, Odai et al. 1995, Park et al. 1998, Panchamoorthy et al. 1996). Both the SH2 and SH3 domains of Grb2 are involved. Cbl has 2 distinct C-terminal domains, proximal and distal. The proximal domain binds Grb2 in resting and stimulated cells, and in stimulated cells also binds Shc. The distal domain can bind the adaptor protein CRKL.<br><br> Tyrosine phosphorylation of Cbl in response to IL-3 releases the SH3 domain of Grb2 which then is free to bind other molecules (Park et al. 1998). <br>Cbl also associates with Fyn (Anderson et al. 1997) and the related kinases Hck and Lyn (Hunter et al. 1999). Binding studies indicate that this binding is independent of the phosphorylation state of Cbl; The association of Fyn with Cbl has been described as constitutive (Hunter et al. 1999).<br><br> Cbl further associates with the p85 subunit of PI3K (Hartley et al. 1995, Anderson et al. 1997, Hunter et al. 1997), this is also described as constitutive and is mediated by the SH3 domain of p85 (Hunter et al. 1997). Edited: Jupe, S, 2010-08-06 Reviewed: Lopez, AF, 2010-09-06 Reviewed: Hercus, TR, 2010-09-06

http://purl.obolibrary.org/obo/HINO_0007497

Authored: Ray, KP, 2010-05-17

Cbl is constitutively associated with Grb2 in resting hematopoietic cells (Anderson et al. 1997, Odai et al. 1995, Park et al. 1998, Panchamoorthy et al. 1996). Both the SH2 and SH3 domains of Grb2 are involved. Cbl has 2 distinct C-terminal domains, proximal and distal. The proximal domain binds Grb2 in resting and stimulated cells, and in stimulated cells also binds Shc. The distal domain can bind the adaptor protein CRKL.

Tyrosine phosphorylation of Cbl in response to IL-3 releases the SH3 domain of Grb2 which then is free to bind other molecules (Park et al. 1998).
Cbl also associates with Fyn (Anderson et al. 1997) and the related kinases Hck and Lyn (Hunter et al. 1999). Binding studies indicate that this binding is independent of the phosphorylation state of Cbl; The association of Fyn with Cbl has been described as constitutive (Hunter et al. 1999).

Cbl further associates with the p85 subunit of PI3K (Hartley et al. 1995, Anderson et al. 1997, Hunter et al. 1997), this is also described as constitutive and is mediated by the SH3 domain of p85 (Hunter et al. 1997).

Edited: Jupe, S, 2010-08-06

Reviewed: Lopez, AF, 2010-09-06

Reviewed: Hercus, TR, 2010-09-06

Pubmed9590251

Pubmed9890970

Pubmed7537740

Pubmed9259313

Pubmed8995358

Reactome, http://www.reactome.org

Pubmed7629144

Pubmed8621719

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

http://purl.obolibrary.org/obo/UniProt_P62993-1

http://purl.obolibrary.org/obo/HINO_0027343

http://purl.obolibrary.org/obo/HINO_0009562

http://purl.obolibrary.org/obo/HINO_0026422

CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated

HINO:0007497

CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated

Reactome Database ID Release 43879917

ReactomeREACT_23799

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