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Atypical protein kinase Cs are the Ras e ... satellite cell differentiation
Atypical protein kinase Cs are the Ras effectors that mediate repression of myogenic satellite cell differentiation.
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Oncogenic Ha-Ras is a potent inhibitor of skeletal muscle cell differentiation, yet the Ras effector mediating this process remains unidentified. Here we demonstrate that the atypical protein kinases (aPKCs; lambda and/or zeta) are downstream Ras effectors responsible for Ras-dependent inhibition of myogenic differentiation in a satellite cell line. First, ectopic expression of Ha-RasG12V induces translocation of PKClambda from the cytosol to the nucleus, suggesting that aPKCs are activated by Ras in myoblasts. The aPKCs function as downstream Ras effectors since inhibition of aPKCs by expression of a dominant negative PKCzeta mutant or by treatment of cells with an inhibitor, GO6983, promotes myogenesis in skeletal muscle satellite cells expressing oncogenic Ha-Ras. Arresting cell proliferation synergistically enhances myogenic differentiation only when aPKCs are also inhibited. Thus, the repression of myogenic differentiation in a satellite cell line appears to be directly mediated by aPKCs acting as Ras effectors and indirectly mediated via stimulation of cell proliferation.
Fedorov YV, Jones NC, Olwin BB
Molecular and cellular biology
2002-02-01 00:00
22
4
1140-9
Animals,Butadienes,Carbazoles,Cell Differentiation,Cell Division,Cell Line,Enzyme Inhibitors,Genes, Reporter,Immunohistochemistry,Indoles,Isoenzymes,Mice,Mitogen-Activated Protein Kinases,Muscle Development,Muscle, Skeletal,Nitriles,Protein Kinase C,Transfection,ras Proteins,Butadienes,Carbazoles,Enzyme Inhibitors,Indoles,Isoenzymes,Nitriles,U 0126,Go 6976,Mitogen-Activated Protein Kinases,Protein Kinase C,ras Proteins
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA
Mol. Cell. Biol.
NIAMS AR39467
0270-7306
852
True
11809805
