Ethanol inhibits insulin receptor tyrosine kinase

Background: Ethanol inhibits insulin-like growth factor-I (IGF-I) and insul in signaling in various cell types. The tyrosine autophosphorylation of the IGF-I and insulin receptors appears to be a target for ethanol, as well as other receptor tyrosine kinases. Methods and Results: The effect of ethanol on purified recombinant insulin receptor kinase activity was examined. A noncompetitive inhibition was obse rved at pharmacologically relevant concentrations of ethanol. Both peptide substrate tyrosine phosphorylation and kinase autophosphorylation are inhib ited by ethanol. Near equivalent inhibition of kinase activity was noted fo r 300 mM methanol, 150 mM ethanol, 20 mM 1-propanol, and 10 mM 1-butanol. Conclusion: The findings identify a direct protein interaction site of etha nol, and provide insight into the mechanism by which ethanol inhibits recep tor tyrosine kinase activity.