Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3).
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Mouton, Véronique, Toussaint, Louise, Vertommen, Didier, Gueuning, Marie-Agnès, Maisin, Liliane, Havaux, Xavier, Sanchez-Canedo, Cossette, Bertrand, Luc, Dequiedt, Franck, Hemmings, Brian Arthur, Hue, Louis and Rider, Mark H (2010) Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3). The Biochemical Journal, 431 (2). pp. 267-275. ISSN 1470-8728
Abstract
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 [γ-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 PKBβ-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 PKBα/β siRNA or PKBα 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 PKBα.
| Item Type: | Article |
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| Additional Information: | unclear |
| Keywords: | glycolysis; protein kinase B (PKB); 6-phosphofructo-2-kinase (PFK-2); serum- and glucocorticoid-induced protein kinase 3 (SGK3); small interfering RNA (siRNA) |
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| Date Deposited: | 04 Dec 2010 00:45 |
| Last Modified: | 01 Feb 2013 00:48 |
| URI: | https://oak.novartis.com/id/eprint/3907 |