Insulin-like growth factor-I-coupled mitogenic signaling in primary cultured human skeletal muscle cells and in C2C12 myoblasts. A central role of protein kinase Cδ
| Autor: | Rita Marincsák, Laszlo Kovacs, István Balázs Tóth, Gabriella Czifra, Peter Acs, Ilona Kovács, Tamás Bíró, Peter M. Blumberg, István Juhász |
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| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Mitosis Desmin Myoblasts Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound medicine Animals Humans Myocyte Elméleti orvostudományok Insulin-Like Growth Factor I Muscle Skeletal Protein kinase A Cells Cultured Protein kinase C Kinase Skeletal muscle Cell Differentiation Orvostudományok Cell Biology musculoskeletal system Molecular biology Cell biology Isoenzymes Protein Kinase C-delta medicine.anatomical_structure chemistry Mitogen-Activated Protein Kinases C2C12 Rottlerin Signal Transduction |
| Zdroj: | Cellular Signalling. 18:1461-1472 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2005.11.007 |
| Popis: | In this study, we have investigated the effects of insulin-like growth factor-I (IGF-I) on cellular responses of primary human skeletal muscle cells and mouse C2C12 myoblasts. In human muscle, IGF-I stimulated proliferation and fusion of the cells and the expression of the differentiation marker desmin. These effects were completely inhibited by Rottlerin, the inhibitor of the protein kinase C (PKC)delta, but were not affected by the inhibition of the mitogen-activated protein kinase (MAPK) or the phosphatidylinositide 3-kinase (PI-3K) pathways. Furthermore, IGF-I initiated the selective translocation of PKCdelta to the nucleus. In C2C12 myoblasts, the growth-promoting effects of IGF-I were abrogated by inhibition of PKCdelta, but not by the inhibition of the PI-3K system. However, in contrast to the human data, the MAPK inhibitor PD098059 partially (yet significantly) also inhibited the action of IGF-I and, furthermore, IGF-I induced phosphorylation of the MAPK Erk-1/2. In addition, overexpression of constitutively active form of PKCdelta in C2C12 cells fully mimicked, whereas overexpression of kinase inactive mutant of the isoform prevented the action of IGF-I. Finally, the inhibition of PKCdelta suspended the IGF-I-induced phosphorylation of Erk-1/2 and, moreover, the inhibition of the MAPK pathway partially (yet significantly) inhibited the accelerated growth of C2C12 cells overexpressing PKCdelta. Taken together, these results demonstrate a novel, central and exclusive involvement of PKCdelta in mediating the action of IGF-I on human skeletal muscle cells, with an additional yet PKCdelta-dependent contribution of the MAPK pathway on C2C12 myoblasts. |
| Databáze: | OpenAIRE |
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