Myogenic differentiation requires signalling through both phosphatidylinositol 3-kinase and p38 MAP kinase

Cell Signal. 2000 Dec;12(11-12):751-7. doi: 10.1016/s0898-6568(00)00120-0.

Abstract

Activation of phosphatidylinositol 3-kinase (PI 3-kinase) or of Akt induces myoblast differentiation. Activation of p38 MAP kinase also triggers myogenic differentiation. The current paper shows that PI 3-kinase and p38 MAP kinase signalling are activated by two separate pathways during myogenic differentiation; both are required for muscle differentiation. p38-induced myogenic differentiation can be inhibited by the PI 3-kinase inhibitor LY294002 without affecting p38 activity. Similarly, a constitutively active form of Akt, myristylated c-Akt (Myr-Akt), induces myogenic differentiation that is inhibited by the p38 inhibitor SB203580. An analysis of the two forms of p38, p38 and p38beta, shows that the activity of both is required for myogenic differentiation. These data suggest that PI 3-kinase and p38 signalling are essential and parallel pathways for myogenic differentiation. They may either affect different downstream targets required for myogenesis or they may converge on shared targets that require input from both signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Differentiation* / drug effects
  • Cell Line
  • Chromones / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter / genetics
  • Humans
  • Imidazoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • MAP Kinase Kinase 6
  • MAP Kinase Signaling System* / drug effects
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Morpholines / pharmacology
  • Muscles / cytology*
  • Muscles / drug effects
  • Muscles / enzymology
  • Muscles / metabolism
  • Mutation / genetics
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myristic Acid / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Pyridines / pharmacology
  • Transcription, Genetic / drug effects
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Chromones
  • Enzyme Inhibitors
  • Imidazoles
  • Isoenzymes
  • Morpholines
  • MyoD Protein
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Pyridines
  • Myristic Acid
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 6
  • MAP2K6 protein, human
  • Map2k6 protein, mouse
  • SB 203580