Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor

Steve T. Russell, Helen L. Eley, Stacey M. Wyke, Michael J. Tisdale

Research output: Contribution to journalArticle

Abstract

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 Ser(473) 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-kappaB (nuclear factor kappaB) 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-kappaB and that this also allows for a specific synthesis of proteasome subunits.
LanguageEnglish
Pages751-759
Number of pages9
JournalBiochemical Journal
Volume409
Issue numberPart 3
DOIs
Publication statusPublished - 1 Feb 2008

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Proteolysis
1-Phosphatidylinositol 4-Kinase
Muscle Proteins
Phosphatidylinositols
Phosphorylation
Phosphotransferases
Proteasome Endopeptidase Complex
Sirolimus
Skeletal Muscle Fibers
Degradation
Chemical activation
Corrosion inhibitors
Ubiquitin
Proteins
70-kDa Ribosomal Protein S6 Kinases
Proto-Oncogene Proteins c-akt
Genistein
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Protein-Tyrosine Kinases
Up-Regulation

Bibliographical note

The final version of record is available at http://www.biochemj.org/bj/409/0751/bj4090751.htm

Keywords

  • Akt/PKB
  • protein kinase B
  • nuclear factor κB
  • NF-κB
  • proteasome expression
  • protein degradation
  • proteolysis-inducing factor
  • PIF)
  • phosphoinositide 3-kinase

Cite this

Russell, Steve T. ; Eley, Helen L. ; Wyke, Stacey M. ; Tisdale, Michael J. / Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor. In: Biochemical Journal. 2008 ; Vol. 409, No. Part 3. pp. 751-759.
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Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor. / Russell, Steve T.; Eley, Helen L.; Wyke, Stacey M.; Tisdale, Michael J.

In: Biochemical Journal, Vol. 409, No. Part 3, 01.02.2008, p. 751-759.

Research output: Contribution to journalArticle

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