Disruption of the availability of amino acids induces a rapid reduction of serine phosphorylation of insulin receptor substrate-1 in vivo and in vitro |
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Authors: | Ohne Yoichiro Toyoshima Yuka Kato Hisanori |
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Institution: | Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo. |
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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. |
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