Subsequent to the binding of insulin to the insulin receptor (IR), present at the cell surface of all the tissues studied so far, conformational change in IR leads to the activation of IR tyrosine kinase. However, the transducer of the signal from IR to its effector(s) is poorly understood, at best. Although GTP-binding proteins (G-proteins) have been implicated in insulin's metabolic actions, a G-protein that directly interacts with IR has not been identified. In the present study, a novel 66 kDa GTP-binding protein, G(ir), has been isolated and characterized. IR and G(ir) from human placental membrane bound to insulin-Sepharose column. GTP as well as GDP (1 mM) eluted G(ir) from the column and acetate buffer (pH 5.0) eluted both IR and G(ir). Both IR and G(ir) thus eluted, absorbed on the anti-IR-Sepharose column and GTP eluted G(ir). Antibodies against synthetic peptides from GTP-binding and ADP-ribosylation domains of G(zα) and G(i-3α), respectively, cross-reacted with G(ir) at various stages of purification. Insulin-activated IR tyrosine kinase phosphorylated G(ir) which was immunoprecipitated by both the antisera. These studies indicate that IR is complexed with G(ir), which could be one of the G-proteins implicated in insulin's signal transduction.
|Original language||English (US)|
|Number of pages||11|
|Journal||Biochemistry and Molecular Biology International|
|State||Published - Jan 1 1994|
ASJC Scopus subject areas
- Molecular Biology