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

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

Stable Identifier

R-HSA-879917

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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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).

Literature References

PubMed ID	Title	Journal	Year
7537740	The proto-oncogene product c-Cbl becomes tyrosine phosphorylated by stimulation with GM-CSF or Epo and constitutively binds to the SH3 domain of Grb2/Ash in human hematopoietic cells Odai, H, Sasaki, K, Iwamatsu, A, Hanazono, Y, Tanaka, T, Mitani, K, Yazaki, Y, Hirai, H	J Biol Chem	1995
8995358	Phosphorylation of Cbl following stimulation with interleukin-3 and its association with Grb2, Fyn, and phosphatidylinositol 3-kinase Anderson, SM, Burton, EA, Koch, BL	J Biol Chem	1997
9590251	CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling Park, RK, Kyono, WT, Liu, Y, Durden, DL	J Immunol	1998
9259313	Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its association with phosphatidylinositol 3-kinase Hunter, S, Koch, BL, Anderson, SM	Mol Endocrinol	1997