The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2 - PubMed (original) (raw)

The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2

M Shaw et al. Biochem J. 1998.

Abstract

Protein kinase B (PKB) isoforms became activated [and glycogen synthase kinase-3 (GSK3) became inhibited] when mouse Swiss 3T3 fibroblasts were exposed to oxidative stress (H2O2) or heat shock, but not when they were exposed to osmotic shock (0.5 M sorbitol or 0. 7 M NaCl), chemical stress (sodium arsenite), the protein-synthesis inhibitor anisomycin, or UV radiation. In contrast, all seven stimuli activated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP-K2). The activation of MAPKAP-K2 was suppressed by the drug SB 203580, but not by inhibitors of phosphoinositide (phosphatidylinositide, PI) 3-kinase. In contrast, the activation of PKB isoforms and the inhibition of GSK3 by oxidative stress or heat shock were prevented by inhibitors of PI 3-kinase, but not by SB 203580. Thus the activation of PKB by oxidative stress or heat shock is mediated by PI 3-kinase and not by MAPKAP-K2. PKBalpha and PKBgamma were also activated by heat shock and oxidative stress in human embryonic kidney 293 cells and PKBgamma was activated by heat shock in NIH 3T3 cells; in each case activation was suppressed by inhibitors of PI 3-kinase. The activation of PKB isoforms by H2O2 may underlie some of the insulin-mimetic effects of this compound.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Nature. 1995 Aug 17;376(6541):599-602 - PubMed
    1. EMBO J. 1996 Dec 2;15(23):6541-51 - PubMed
    1. Trends Cell Biol. 1997 Sep;7(9):353-61 - PubMed
    1. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4173-7 - PubMed
    1. Curr Biol. 1997 Oct 1;7(10):776-89 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources