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

被引:29
作者
Czifra, Gabriella
Toth, Istvan Balazs
Marincsak, Rita
Juhasz, Istvan
Kovacs, Ilona
Acs, Peter
Kovacs, Laszlo
Blumberg, Peter A.
Biro, Tamas
机构
[1] Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, H-4012 Debrecen, Hungary
[2] Univ Debrecen, Cell Physiol Res Grp, Hungarian Acad Sci, Med & Hlth Sci Ctr,Res Ctr Mol Med, H-4012 Debrecen, Hungary
[3] Univ Debrecen, Res Ctr Mol Med, Dept Dermatol, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary
[4] Kenezy Cty Hosp, Dept Pathol, Debrecen, Hungary
[5] NCI, Mol Mech Tumor Promot Sect, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD USA
基金
匈牙利科学研究基金会;
关键词
human skeletal muscle; C2C12; cells; insulin-like growth factor-I (IGF-I); protein kinase C (PKC); PKC delta; mitogen-activated protein kinase (MAPK); proliferation;
D O I
10.1016/j.cellsig.2005.11.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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)6, 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 PKC delta to the nucleus. In C2C12 myoblasts, the growth-promoting effects of lGF-I were abrogated by inhibition of PKC delta, 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 PKC6 in C2C12 cells fully mimicked, whereas overexpression of kinase inactive mutant of the isoform prevented the action of IGF-I. Finally, the inhibition of PKC6 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 PKC delta. Taken together, these results demonstrate a novel, central and exclusive involvement of PKC6 in mediating the action of IGF-I on human skeletal muscle cells, with an additional yet PKC delta-dependent contribution of the MAPK pathway on C2C12 myoblasts. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1461 / 1472
页数:12
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