The p38 pathway regulates Akt both at the protein and transcriptional activation levels during myogenesis.
The molecular signalling pathways governing skeletal muscle differentiation remain unclear. Recent work has demonstrated that both the phosphatidylinositol 3-kinase (PI3K)/Akt and p38 pathways play important roles in myogenesis. Here, we describe the interactions between these pathways in C2C12 cells. Overall, our results suggest that Akt acts downstream of p38 in myogenic cell differentiation. Activating the p38 pathway results in the concurrent activation of Akt; conversely, activating Akt does not affect p38. We have analysed Akt messenger RNA and protein levels in a C2C12 cell line stably expressing a dominant negative (DN) form of the p38 activator MKK3. Compared to control cells, this cell line exhibits reduced levels of Akt messenger RNA and total protein. In addition, blocking the p38 pathway during differentiation inhibits Akt activation. Our results show for the first time that p38 can directly affect Akt at the transcriptional level as well as at the protein activation level during myogenic differentiation.
Cabane
Candice
C
UMR 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
Coldefy
Anne-Sophie
AS
Yeow
Karen
K
Dérijard
Benoît
B
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D015151:Immunoblotting; D051379:Mice; D008954:Models, Biological; D009132:Muscles / Q000166:cytology* / Q000201:enzymology*; D018008:Myogenin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D018008:Myogenin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C503801:Myog protein, mouse