| 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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MedLine Citation:
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PMID: 20687898 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Véronique Mouton; Louise Toussaint; Didier Vertommen; Marie-Agnès Gueuning; Liliane Maisin; Xavier Havaux; Cossette Sanchez-Canedo; Luc Bertrand; Franck Dequiedt; Brian A Hemmings; Louis Hue; Mark H Rider |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 431 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2010-10-13 Revised Date: 2011-09-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 267-75 Citation Subset: IM |
Affiliation:
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Université catholique de Louvain and de Duve Institute, 75 Avenue Hippocrate, Brussels, Belgium. |
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| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Chemical | |
Reg. No./Substance:
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0/Protein Kinase Inhibitors; 11061-68-0/Insulin; EC 2.7.1.105/Phosphofructokinase-2; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/SGK3 protein, human; EC 2.7.11.2/pyruvate dehydrogenase (acetyl-transferring) kinase |
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