Effects of PI3K catalytic subunit and Akt isoform deficiency on mTOR and p70S6K activation in myoblasts

Ronald W. Matheny, Martin L Adamo

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The PI3K/Akt/mTOR signaling pathway is critical for cellular growth and survival in skeletal muscle, and is activated in response to growth factors such as insulin-like growth factor-I (IGF-I). We found that in C2C12 myoblasts, deficiency of PI3K p110 catalytic subunits or Akt isoforms had distinct effects on phosphorylation of mTOR and p70S6K. siRNA-mediated knockdown of PI3K p110α, p110β, and simultaneous knockdown of p110α and p110β resulted in increased basal and IGF-I-stimulated phosphorylation of mTOR S2448 and p70S6K T389; however, phosphorylation of S6 was reduced in p110β-deficient cells, possibly due to reductions in total S6 protein. We found that IGF-I-stimulated Akt1 activity was enhanced in Akt2- or Akt3-deficient cells, and that knockdown of individual Akt isoforms increased mTOR/p70S6K activation in an isoform-specific fashion. Conversely, levels of IGF-I-stimulated p70S6K phosphorylation in cells simultaneously deficient in both Akt1 and Akt3 were increased beyond those seen with loss of any single Akt isoform, suggesting an alternate, Akt-independent mechanism that activates mTOR/p70S6K. Our results collectively suggest that mTOR/p70S6K is activated in a PI3K/Akt-dependent manner, but that in the absence of p110α or Akt, alternate pathway(s) may mediate activation of mTOR/p70S6K in C2C12 myoblasts.

Original languageEnglish (US)
Pages (from-to)252-257
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number2
DOIs
StatePublished - Dec 11 2009

Fingerprint

70-kDa Ribosomal Protein S6 Kinases
Myoblasts
Phosphatidylinositol 3-Kinases
Catalytic Domain
Protein Isoforms
Chemical activation
Phosphorylation
Insulin-Like Growth Factor I
S 6
Critical Pathways
Small Interfering RNA
Muscle
Intercellular Signaling Peptides and Proteins
Skeletal Muscle
Growth

Keywords

  • Akt
  • mTOR
  • Myoblast
  • PI3K
  • S6K

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Effects of PI3K catalytic subunit and Akt isoform deficiency on mTOR and p70S6K activation in myoblasts. / Matheny, Ronald W.; Adamo, Martin L.

In: Biochemical and Biophysical Research Communications, Vol. 390, No. 2, 11.12.2009, p. 252-257.

Research output: Contribution to journalArticle

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