Transforming growth factor beta activates Rac1 and Cdc42Hs GTPases and the JNK pathway in skeletal muscle cells.
The transforming growth factor beta (TGFbeta) plays an important role in cell growth and differentiation. However, the intracellular signaling pathways through which TGFbeta inhibits skeletal myogenesis remain largely undefined. By measuring GTP-loading of Rho GTPases and the organization of the F-actin cytoskeleton and the plasma membrane, we analyzed the effect of TGFbeta addition on the activity of three GTPases, Rac1, Cdc42Hs and RhoA. We report that TGFbeta activates Rac1 and Cdc42Hs in skeletal muscle cells, two GTPases previously described to inhibit skeletal muscle cell differentiation whereas it inactivates RhoA, a positive regulator of myogenesis. We further show that TGFbeta activates the C-jun N-terminal kinases (JNK) pathway in myoblastic cells through Rac1 and Cdc42Hs GTPases. We propose that the activation of Rho family proteins Rac1 and Cdc42Hs which subsequently regulate JNK activity participates in the inhibition of myogenesis by TGFbeta.
Meriane
Mayya
M
Centre de recherche de biochimie macromoléculaire (CRBM), CNRS UPR 1086, IFR24, 1919, route de Mende, 34293 cedex, Montpellier, France.
Charrasse
Sophie
S
Comunale
Franck
F
Gauthier-Rouvière
Cécile
C
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032342:Muscle Cells / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D016212:Transforming Growth Factor beta; C081345:Cdc42Hs-associated kinase; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins