Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor
| Autor: | Steven T. Russell, Helen L. Eley, Stacey M. Wyke, Michael J. Tisdale |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Muscle Fibers
Skeletal Muscle Proteins Protein degradation Biochemistry mTORC2 Cell Line Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Animals LY294002 Phosphorylation Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Phosphoinositide 3-kinase biology Ubiquitin Chemistry Akt/PKB signaling pathway TOR Serine-Threonine Kinases Cell Biology Molecular biology Cell biology biology.protein Proteoglycans Protein Kinases Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical Journal. 409:751-759 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20070688 |
| Popis: | In the present study the role of Akt/PKB (protein kinase B) in PIF- (proteolysis-inducing factor) induced protein degradation has been investigated in murine myotubes. PIF induced transient phosphorylation of Akt at Ser473 within 30 min, which was attenuated by the PI3K (phosphoinositide 3-kinase) inhibitor LY294002 and the tyrosine kinase inhibitor genistein. Protein degradation was attenuated in myotubes expressing a dominant-negative mutant of Akt (termed DNAkt), compared with the wild-type variant, whereas it was enhanced in myotubes containing a constitutively active Akt construct (termed MyrAkt). A similar effect was observed on the induction of the ubiquitin–proteasome pathway. Phosphorylation of Akt has been linked to up-regulation of the ubiquitin–proteasome pathway through activation of NF-κB (nuclear factor κB) in a PI3K-dependent process. Protein degradation was attenuated by rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin), when added before, or up to 30 min after, addition of PIF. PIF induced transient phosphorylation of mTOR and the 70 kDa ribosomal protein S6 kinase. These results suggest that transient activation of Akt results in an increased protein degradation through activation of NF-κB and that this also allows for a specific synthesis of proteasome subunits. |
| Databáze: | OpenAIRE |
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