Rap1A protein interferes with various MAP kinase activating pathways in skeletal myogenic cells.
Constitutive expression of the activated Rap1A protein inhibits differentiation of myogenic C2 cells whereas the inactivated Rap1A protein favours cell differentiation and induces late endocytic compartments clustering. Although the role of Rap1A in MAPK activation has been analysed in various cell types, the signalling pathways activated by Rap1A have not been explored in myogenic cells. In this study, we investigated MAP kinase activity in control C2 myoblasts and in stable C2 cell lines expressing mutated Rap1A proteins. We provide evidence that Rap1A mutants promote ERK activation and that the active protein induces a more sustained activation than the inactive protein. In addition, we established that various pathways mediate transient ERK activation in control cells and in cells expressing the inactivated Rap1A protein. In these cells, ERK are activated by a Raf/MEK-dependent pathway, a P13K/Raf-independent pathway and a third undetermined pathway. In cells expressing the activated Rap1A protein, a PI3K/Raf/MEK-dependent pathway mediates transient ERK activation. However, MAPK activation appears more complex since, according to the state of the myoblasts or the duration of MAPK stimulation, we observed that Rap1A protein could interfere or not with ERK activation.
Pizon
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V
Institut André Lwoff, UPR 1983, Villejuif, France.
Baldacci
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G
D000730:Androstadienes / Q000494:pharmacology; D001798:Blood Proteins / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000730:Androstadienes; D001798:Blood Proteins; D000242:Cyclic AMP; D005419:Flavonoids; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; D020827:rap1 GTP-Binding Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one