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The p38 pathway regulates Akt both at the protein and transcriptional activation levels during myogenesis

Candice Cabane1, Anne-Sophie Coldefy, Karen Yeow

  • 1UMR CNRS 6548, Laboratoire de Physiologie Cellulaire et Moléculaire, Université de Nice-Sophia Antipolis, Faculté des Sciences, 28 Avenue Valrose, 06108 Nice, France. derijard@unice.fr

Cellular Signalling
|September 24, 2004
PubMed

Insights

The p38 pathway regulates skeletal muscle differentiation by activating phosphatidylinositol 3-kinase (PI3K)/Akt. This study reveals p38 influences Akt transcription and activation, clarifying their interaction in myogenesis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Muscle Development

Background:

  • Skeletal muscle differentiation (myogenesis) involves complex molecular signaling pathways.
  • Both phosphatidylinositol 3-kinase (PI3K)/Akt and p38 pathways are implicated in myogenesis.
  • The precise interaction between these pathways in muscle cell differentiation is not fully understood.

Purpose of the Study:

  • To elucidate the interaction between the PI3K/Akt and p38 signaling pathways during myogenesis.
  • To determine the regulatory relationship between p38 and Akt in C2C12 myoblasts.

Main Methods:

  • Utilized C2C12 cells, a common model for skeletal muscle differentiation.
  • Employed a stable cell line expressing a dominant-negative (DN) form of MKK3, a p38 activator.
  • Analyzed Akt messenger RNA (mRNA) and protein levels.
  • Investigated the effect of p38 pathway activation/inhibition on Akt activation during differentiation.

Main Results:

  • Akt acts downstream of p38 in the context of myogenic cell differentiation.
  • Activation of the p38 pathway led to concurrent activation of Akt, but Akt activation did not affect p38.
  • Inhibition of the p38 pathway reduced Akt mRNA and total protein levels and blocked Akt activation during differentiation.

Conclusions:

  • The p38 pathway directly influences Akt at both the transcriptional and protein activation levels during myogenic differentiation.
  • These findings establish a novel regulatory link where p38 signaling is upstream of Akt in skeletal muscle development.
  • This study provides critical insights into the molecular mechanisms governing myogenesis.

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