An essential role of phosphatidylinositol 3-kinase in myogenic differentiation

Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14179-83. doi: 10.1073/pnas.95.24.14179.

Abstract

The oncogene p3k, coding for a constitutively active form of phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137), strongly enhances myogenic differentiation in cultures of chicken-embryo myoblasts. It increases the size of the myotubes and induces elevated levels of the muscle-specific proteins MyoD, myosin heavy chain, creatine kinase, and desmin. Inhibition of PI 3-kinase activity with LY294002 or with dominant-negative mutants of PI 3-kinase interferes with myogenic differentiation and with the induction of muscle-specific genes. PI 3-kinase is therefore an upstream mediator for the expression of the muscle-specific genes and is both necessary and rate-limiting for the process of myogenesis.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Chick Embryo
  • Chromones / pharmacology
  • Creatine Kinase / genetics
  • Desmin / genetics
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation
  • Morpholines / pharmacology
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / enzymology
  • MyoD Protein / genetics
  • Myosin Heavy Chains / genetics
  • Oncogenes
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*

Substances

  • Chromones
  • Desmin
  • Enzyme Inhibitors
  • Morpholines
  • MyoD Protein
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Creatine Kinase
  • Myosin Heavy Chains