HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells
HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells
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DOI：
10.1016/j.mce.2011.06.029
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发表时间：
2011-09-15
影响因子：
4.1
通讯作者：
Takahashi, Shin-Ichiro
中科院分区：
文献类型：
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作者：
Fukushima, Toshiaki;Okajima, Hiroshi;Takahashi, Shin-Ichiro
包括促甲状腺激素(TSH)或cAMP类似物在内的cAMP生成剂长期刺激FRTL-5甲状腺细胞，可增强胰岛素样生长因子(IGF)-I触发的胰岛素受体底物(IRS)-2的酪氨酸磷酸化，从而促进IGF-I依赖的增殖。由于我们鉴定了HSP90是一种IRS-2相互作用蛋白，因此我们研究了HSP90在IRS-2增强IGF信号中的作用。我们发现，长时间的二丁酰cAMP处理诱导IRS-2丝氨酸/苏氨酸磷酸化。使用HSP90伴侣活性的特异性抑制剂格尔达那霉素或针对HSP90的小干扰RNA，我们发现HSP90介导了cAMP诱导的IRS-2的丝氨酸/苏氨酸磷酸化。此外，在二丁酰cAMP处理细胞24小时时，格尔达霉素对HSP90的抑制抑制了IGF-I诱导的IRS-2酪氨酸磷酸化的cAMP依赖的增强。综上所述，我们得出结论：HSP90与IRS-2相互作用，通过其伴侣活性介导cAMP依赖的丝氨酸/苏氨酸磷酸化IRS-2，从而增强IGF-I诱导的IRS-2酪氨酸磷酸化。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
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 24 h 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.