An essential role of phosphatidylinositol 3-kinase in myogenic differentiation.
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.
Jiang
B H
BH
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Zheng
J Z
JZ
Vogt
P K
PK
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002867:Chromones / Q000494:pharmacology; D003402:Creatine Kinase / Q000235:genetics; D003893:Desmin / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D009025:Morpholines / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology; D017570:MyoD Protein / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*
D002867:Chromones; D003893:Desmin; D004791:Enzyme Inhibitors; D009025:Morpholines; D017570:MyoD Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D003402:Creatine Kinase; D018995:Myosin Heavy Chains