Reference : Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), bu...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/78031
Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3).
English
Mouton, Veronique [> > > >]
Toussaint, Louise mailto [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc. >]
Vertommen, Didier [> > > >]
Gueuning, Marie*-Agnes [> > > >]
Maisin, Liliane [> > > >]
Havaux, Xavier [> > > >]
Sanchez-Canedo, Cossette [> > > >]
Bertrand, Luc [> > > >]
Dequiedt, Franck mailto [Université de Liège - ULg > > GIGA-Research - Centre de Bio. Fond. - Section de Biologie cell. et moléc. >]
Hemmings, Brian A [> > > >]
Hue, Louis [> > > >]
Rider, Mark H [> > > >]
2010
Biochemical Journal
Portland Press
431
2
267-75
International
0264-6021
1470-8728
London
United Kingdom
[en] Animals ; Binding Sites ; Cattle ; Cell Line ; Enzyme Activation/drug effects ; Humans ; Insulin/pharmacology ; Male ; Mice ; Mice, Transgenic ; Mutation/genetics ; Myocardium/cytology/enzymology ; Myocytes, Cardiac/drug effects/enzymology ; Organ Specificity/drug effects ; Phosphofructokinase-2/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/deficiency/metabolism ; Rats ; Rats, Wistar ; Substrate Specificity/drug effects
[en] On the basis of transfection experiments using a dominant-negative approach, our previous studies suggested that PKB (protein kinase B) was not involved in heart PFK-2 (6-phosphofructo2-kinase) activation by insulin. Therefore we first tested whether SGK3 (serum- and glucocorticoid-induced protein kinase 3) might be involved in this effect. Treatment of recombinant heart PFK-2 with [gamma-32P]ATP and SGK3 in vitro led to PFK-2 activation and phosphorylation at Ser466 and Ser483. However, in HEK-293T cells [HEK (human embryonic kidney)-293 cells expressing the large T-antigen of SV40 (simian virus 40)] co-transfected with SGK3 siRNA (small interfering RNA) and heart PFK-2, insulin-induced heart PFK-2 activation was unaffected. The involvement of PKB in heart PFK-2 activation by insulin was re-evaluated using different models: (i) hearts from transgenic mice with a muscle/heart-specific mutation in the PDK1 (phosphoinositide-dependent protein kinase 1)-substrate-docking site injected with insulin; (ii) hearts from PKBbeta-deficient mice injected with insulin; (iii) freshly isolated rat cardiomyocytes and perfused hearts treated with the selective Akti-1/2 PKB inhibitor prior to insulin treatment; and (iv) HEK-293T cells co-transfected with heart PFK-2, and PKBalpha/beta siRNA or PKBalpha siRNA, incubated with insulin. Together, the results indicated that SGK3 is not required for insulin-induced PFK-2 activation and that this effect is likely mediated by PKBalpha.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/78031
10.1042/BJ20101089

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