The effectors that have been characterized to bind IRS proteins include phosphatidyl-inositol-3-kinases (PI3K), Growth factor receptor-bound protein 2 (Grb2), SH2 domain-containing tyrosine phosphatase (SHP-2), Fyn, cellular CT10 regulator of kinase (c-Crk), among others, all of which intervene as mediators in metabolic functions and in insulin growth promoter functions (17).
A self-attenuated mechanism to negatively regulate the function of IRS proteins.
Phosphorylated IRS proteins
act as docking sites for several intracellular proteins such as Grb2, NcK and the regulatory subunit p85 of phosphatidylinositol 3-Kinase (PI3K), which mediate different actions of insulin.
Important signaling molecules downstream of IRS proteins
and Shc include MAPK and PI3K (Saltiel et al.
The IRS proteins
are cytoplasmic proteins, with multiple tyrosine phosphorylation sites, and phosphorylation of IRS proteins
has been implicated as the first post receptor step in insulin signal transmission.
It is possible that the interaction between JAK2 and IRS proteins
is mediated via a focal adhesion kinase, FAK (Zhu et al.