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Ethanol inhibits insulin receptor tyrosine kinase
A E Seiler1, A Henderson, R Rubin
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Background:
Ethanol inhibits insulin-like growth factor-I (IGF-I) and insulin 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 observed at pharmacologically relevant concentrations of ethanol. Both peptide substrate tyrosine phosphorylation and kinase autophosphorylation are inhibited by ethanol. Near equivalent inhibition of kinase activity was noted for 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 ethanol, and provide insight into the mechanism by which ethanol inhibits receptor tyrosine kinase activity.