Functional importance of heat shock protein 90 associated with insulin receptor on insulin-stimulated mitogenesis.
The role of stress proteins on the function of insulin receptor is not well understood. In the rat-1 fibroblasts overexpressing human insulin receptors, heat shock protein (Hsp) 90 was co-immunoprecipitated with insulin receptors and the association was not affected by insulin stimulation. A GST-fusion protein containing the intracellular insulin receptor beta subunit was associated with Hsp 90 in vitro, suggesting the direct interaction of this protein with insulin receptor beta-subunit. Furthermore, microinjection of anti-Hsp 90 antibody into these cells completely inhibited insulin-stimulated mitogenesis. However, neither epidermal growth factor-stimulated nor serum-stimulated mitogenic signal in the cells was affected by the antibody microinjection. These results suggest that Hsp 90 constitutively binds to insulin receptor beta-subunit, which may be necessary for insulin signaling in mitogenesis.
Takata
Y
Y
First Department of Medicine, Toyama Medical and Pharmaceutical University, Sugitani Toyama, 930-01, Japan.
Imamura
T
T
Iwata
M
M
Usui
I
I
Haruta
T
T
Nandachi
N
N
Ishiki
M
M
Sasaoka
T
T
Kobayashi
M
M
D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008845:Microinjections; D008934:Mitogens / Q000494:pharmacology*; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494371:HSPA8 protein, human; C494373:Hspa8 protein, rat; D007328:Insulin; D008934:Mitogens; D011972:Receptor, Insulin