HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells

T Fukushima, H Okajima, D Yamanaka, M Ariga… - Molecular and cellular …, 2011 - Elsevier
T Fukushima, H Okajima, D Yamanaka, M Ariga, S Nagata, A Ito, M Yoshida, T Asano…
Molecular and cellular endocrinology, 2011Elsevier
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 …
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.
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