Myogenic differentiation requires signalling through both phosphatidylinositol 3-kinase and p38 MAP kinase.
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.
Li
Y
Y
Department of Immunology, IMM-9, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jiang
B
B
Ensign
W Y
WY
Vogt
P K
PK
Han
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048669:MAP Kinase Kinase 6; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D019814:Myristic Acid / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002867:Chromones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D048669:MAP Kinase Kinase 6; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D017570:MyoD Protein; D019814:Myristic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human; C482566:MAP2K6 protein, human; C482567:Map2k6 protein, mouse; C093642:SB 203580