Inhibition of insulin-like growth factor I receptor tyrosine kinase by ethanol.

Ethanol inhibits insulin and insulin-like growth factor-I (IGF-I) signaling in a variety of cell types leading to reduced mitogenesis and impaired survival. This effect is associated with inhibition of insulin receptor (IR) and insulin-like growth factor-I receptor (IGF-IR) autophosphorylation, which implicates these receptors as direct targets for ethanol. It was demonstrated previously that ethanol inhibits the autophosphorylation and kinase activity of the purified cytoplasmic tyrosine kinase domain of the IR.

Ethanol inhibits palmitoylation of G protein G alpha(s).

Neurobiological actions of ethanol have been linked to perturbations in cyclic AMP (cAMP)-dependent signaling processes. Chronic ethanol exposure leads to desensitization of cAMP production in response to physiological ligands (heterologous desensitization). Ethanol-induced alterations in neuronal expression of G proteins G(s) and G(i) have been invoked as a cause of heterologous desensitization.

Epidermal growth factor-induced activation of the insulin-like growth factor I receptor in rat hepatocytes.

Insulin-like growth factor I (IGF-I) plays a critical role in the induction of cell cycle progression and survival in many cell types. However, there is minimal IGF-I binding to hepatocytes, and a role for IGF-I in hepatocyte signaling has not been elucidated. The dynamics of IGF-I receptor (IGF-IR) activation were examined in freshly isolated rat hepatocytes.