Premium
Heat shock protein‐90 dampens and directs signaling stimulated by insulin‐like growth factor‐1 and insulin
Author(s) -
Meares Gordon P.,
Zmijewska Anna A.,
Jope Richard S.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.026
Subject(s) - insulin , heat shock protein , shock (circulatory) , insulin receptor , insulin like growth factor , growth factor , medicine , endocrinology , microbiology and biotechnology , chemistry , biology , receptor , biochemistry , insulin resistance , gene
Heat shock protein‐90 (Hsp90) buffers cells from genetic mutations and environmental stresses. To test if this capability reflects a normal physiological function of Hsp90 to buffer cellular signals, the effects of Hsp90 inhibition were measured on activation of Akt. Inhibition of Hsp90 with geldanamycin amplified Akt phosphorylation induced by insulin‐like growth factor‐1 (IGF‐1) or insulin, indicating that Hsp90 normally buffers these signals. Furthermore, with IGF‐1 stimulation Hsp90 inhibition increased p38 activation, produced additive activation of p90RSK, and slightly increased the duration of ERK1/2 activation. Hsp90 dampened Akt signaling by facilitating phosphatase‐mediated dephosphorylation of Akt. Thus, Hsp90 not only buffers the cellular effects of mutations and stresses, but also buffers the magnitude and duration of activation of proliferative and survival‐promoting signaling responses.