Ethanol inhibits insulin receptor tyrosine kinase.
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.


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.


CONCLUSIONS
The findings identify a direct protein interaction site of ethanol, and provide insight into the mechanism by which ethanol inhibits receptor tyrosine kinase activity.
Seiler
A E
AE
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Henderson
A
A
Rubin
R
R
D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D000431:Ethanol; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases