HSP90 interacting with IRS-2 is involved in cAMP-dependent potentiation of IGF-I signals in FRTL-5 cells
| Autor: | Fukushima, Toshiaki, Okajima, H., Yamanaka, D., Ariga, M., Nagata, S., Ito, A., Yoshida, M., Asano, T., Chida, K., Hakuno, F., Takahashi, S. |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Biochemistry Cell Line chemistry.chemical_compound Endocrinology Insulin-Like Growth Factor I/*pharmacology/physiology HSP90 Heat-Shock Proteins/genetics/*metabolism Internal medicine Insulin receptor substrate Cyclic AMP polycyclic compounds medicine Animals Immunoprecipitation Protein phosphorylation HSP90 Heat-Shock Proteins Insulin-Like Growth Factor I Phosphorylation Threonine Molecular Biology Insulin Receptor Substrate Proteins/genetics/*metabolism biology Cyclic AMP/*pharmacology/physiology Tyrosine phosphorylation Geldanamycin Hsp90 Signal Transduction Rats Cell biology chemistry Gene Knockdown Techniques Insulin Receptor Substrate Proteins biology.protein RNA Interference PMSF Protein Binding |
| Zdroj: | Molecular and Cellular Endocrinology. 344:81-89 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2011.06.029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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