Dynamin associates with Src-Homology Collagen (Shc) and becomes tyrosine phosphorylated in response to insulin.

The activated insulin receptor phosphorylates docking proteins such as Src-Homology Collagen (Shc) and Insulin Receptor Substrate-1 (IRS-1), which then bind several proteins that contain a Src-Homology 2 (SH2) domain. Both Shc and IRS-1 associate with Growth Factor Receptor-Bound protein 2 (Grb2), an adaptor molecule. The hormone-receptor complex is then rapidly internalized through coated-pits.

p125Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors.

The focal adhesion kinase p125(Fak) is a widely expressed cytosolic tyrosine kinase, which is involved in integrin signaling and in signal transduction of a number of growth factors. In contrast to tyrosine kinase receptors such as the platelet-derived growth factor and the hepatocyte growth factor receptors, which induce p125(Fak) phosphorylation, insulin has been shown to promote its dephosphorylation. In this study, we compared p125(Fak) phosphorylation in insulin-stimulated cells maintained in suspension or in an adhesion state.

Role of the insulin receptor C-terminal acidic domain in the modulation of the receptor kinase by polybasic effectors.

Basic polymers such as polylysine have been found to activate insulin receptor autophosphorylation and kinase activity toward substrates. It was suggested that acidic receptor domains may be involved in the interaction of the receptor with these basic effectors. In a previous study, we have shown that the receptor acid-rich C-terminal sequence, including residues 1270-1280, is involved in the regulation of the receptor kinase activity.

Insulin receptor-induced phosphorylation of cellular and synthetic substrates is regulated by the receptor beta-subunit C-terminus.

The transmembrane beta-subunits of the insulin receptor possess hormone-sensitive tyrosine kinase activity. To study the role of the C-terminus domain, a rabbit antipeptide antibody directed to the 1294-1317 domain was produced. The antipeptide antibody inhibited the receptor-induced phosphorylation of poly (Glu, Tyr) and synthetic peptides corresponding to the receptor autophosphorylation sites.

A conformational change in the beta-subunit of the insulin-like growth factor I receptor identified by antipeptide antibodies.

Insulin-like growth factor I (IGF-I) binding to its receptor results in receptor autophosphorylation and phosphorylation of several cellular substrates. The mechanism by which binding of the ligand to the extracellular receptor domain activates the intracellular kinase remains to be defined. Using polyclonal antibodies against four regions of the IGF-I receptor, we searched for putative conformational changes occurring in purified receptors.