title: HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells.
abstract: Prolonged stimulation of FRTL-5 thyroid cells with cAMP-generating agents including thyroid-stimulating hormone (TSH) or cAMP analogues potentiates tyrosine phosphorylation of insulin receptor substrate (IRS)-2 triggered by insulin-like growth factor (IGF)-I, leading to enhancement of IGF-I-dependent proliferation. Because we identified HSP90 as an IRS-2-interacting protein, the roles of HSP90 in potentiation of IGF signals through IRS-2 were investigated. We found that prolonged dibutyryl cAMP treatment induced serine/threonine phosphorylation of IRS-2. Using a specific inhibitor of HSP90 chaperone activity, geldanamycin, or small interfering RNA against HSP90, we showed that HSP90 mediates cAMP-induced serine/threonine phosphorylation of IRS-2. Furthermore, inhibition of HSP90 by geldanamycin during dibutyryl cAMP pretreatment of cells for 24h suppressed cAMP-dependent potentiation of tyrosine phosphorylation of IRS-2 induced by IGF-I. Taking together, we conclude that HSP90 interacting with IRS-2 mediates cAMP-dependent serine/threonine phosphorylation of IRS-2 via its chaperone activity, leading to potentiation of tyrosine phosphorylation of IRS-2 induced by IGF-I.
authors: Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors: Toshiaki
authors: T
authors: Fukushima
authors: Hiroshi
authors: H
authors: Okajima
authors: Daisuke
authors: D
authors: Yamanaka
authors: Miyako
authors: M
authors: Ariga
authors: Shinji
authors: S
authors: Nagata
authors: Akihiro
authors: A
authors: Ito
authors: Minoru
authors: M
authors: Yoshida
authors: Tomoichiro
authors: T
authors: Asano
authors: Kazuhiro
authors: K
authors: Chida
authors: Fumihiko
authors: F
authors: Hakuno
authors: Shin-Ichiro
authors: S
authors: Takahashi
mesh_terms: D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology* / Q000502:physiology; D055785:Gene Knockdown Techniques; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction
chemical_list: D018841:HSP90 Heat-Shock Proteins; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP