title: Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1.
abstract: In 3T3-L1 adipocytes, insulin or anisomycin stimulated phosphorylation of IRS-1 at Ser(307) and Ser(636/639), both of which were partially reduced by the mTOR inhibitor, rapamycin, or the JNK inhibitor, SP600125, and were further inhibited by a combination of them. Interestingly, anisomycin-induced p70(S6K) phosphorylation was reduced by SP600125, while insulin-induced p70(S6K) phosphorylation was not. Furthermore, unlike insulin, anisomycin failed to elicit translocation or degradation of IRS-1. These results indicate that mTOR and JNK play roles in phosphorylating IRS-1 serine residues, and that insulin and anisomycin are different in terms of the relationship of activation between mTOR and JNK, and the effects on IRS-1 localization and stability.
authors.affiliation: First Department of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiratani
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Haruta
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tani
authors.forename: Junko
authors.initials: J
authors.lastname: Kawahara
authors.forename: Isao
authors.initials: I
authors.lastname: Usui
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D006868:Hydrolysis; D055504:Insulin Receptor Substrate Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D021381:Protein Transport; D012694:Serine / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D012694:Serine; D000841:Anisomycin; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases