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Ethanol Inhibits Insulin Receptor Tyrosine Kinase
Author(s) -
Seiler Andrea E. M.,
Henderson Aaron,
Rubin Raphael
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb01992.x
Subject(s) - autophosphorylation , insulin receptor , irs2 , receptor tyrosine kinase , tyrosine kinase , chemistry , tyrosine phosphorylation , insulin receptor substrate , tropomyosin receptor kinase c , biochemistry , platelet derived growth factor receptor , insulin , tyrosine , phosphorylation , biology , receptor , endocrinology , protein kinase a , insulin resistance , growth factor
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.