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

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).

Cbl蛋白在静息造血细胞中与Grb2蛋白构成性相关（参见Anderson等，1997年，Odai等，1995年，Park等，1998年，Panchamoorthy等，1996年）。Grb2的SH2和SH3结构域均参与此过程。Cbl蛋白具有两个不同的C端结构域，近端和远端。近端结构域在静息和激活细胞中与Grb2结合，并在激活细胞中亦与Shc结合。远端结构域可结合适配蛋白CRKL。

在IL-3刺激下，Cbl的酪氨酸磷酸化释放Grb2的SH3结构域，使其能够自由结合其他分子（参见Park等，1998年）。

Cbl还与Fyn蛋白（参见Anderson等，1997年）及其相关激酶Hck和Lyn（参见Hunter等，1999年）相关联。结合研究表明，这种结合状态不受Cbl磷酸化状态的制约；Fyn与Cbl的结合已被描述为构成性（参见Hunter等，1999年）。

此外，Cbl还与PI3K的p85亚基相关联（参见Hartley等，1995年，Anderson等，1997年，Hunter等，1997年），这一过程亦被描述为构成性，并由p85的SH3结构域介导（参见Hunter等，1997年）。