title: Disruption of the availability of amino acids induces a rapid reduction of serine phosphorylation of insulin receptor substrate-1 in vivo and in vitro.
abstract: Insulin receptor substrate-1 (IRS-1) plays a pivotal role in insulin signal transduction. It has been shown that the amino acids modulate insulin signaling at the level of IRS-1. Here we show that an amino acid unbalanced diet causes a reduction in serine phosphorylation as well as an elevation in insulin-induced tyrosine phosphorylation of IRS-1 in rat muscle. In fibroblasts and myotube cells, the effect of amino acid deprivation on IRS-1 phosphorylation was evident only when cells were pretreated with reagents causing hyperphosphorylation of serines of IRS-1. But, the target kinases of these reagents were not inactivated by amino acid deprivation, suggesting that amino acid deprivation activates serine/threonine phosphatase(s) of IRS-1. The phosphatases regulated by mammalian target of rapamycin do not appear to participate in the dephosphorylation either. These results suggest that amino acid deprivation dephosphorylates IRS-1 through unidentified serine/threonine phosphatases and thereby potentiates insulin signaling.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Ohne
authors.forename: Yuka
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kato
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D019319:Okadaic Acid; D010750:Phosphoproteins / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D019319:Okadaic Acid; D012694:Serine; D010744:Phosphoric Monoester Hydrolases