Protein kinase C signaling controls skeletal muscle fiber types

被引:18
作者
DiMario, JX [1 ]
机构
[1] Finch Univ Hlth Sci Chicago Med Sch, Dept Cell Biol & Anat, N Chicago, IL 60064 USA
关键词
D O I
10.1006/excr.2000.5094
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Slow myosin heavy chain 2(MyHC2) gene expression in fetal avian skeletal muscle fibers is regulated by innervation and protein kinase C (PKC) activity. Fetal chick muscle fibers derived from the slow twitch medial adductor (RIA) muscle express slow MyHC2 when innervated in vitro. The same pattern of slow MyHC2 regulation occurs in MA muscle fibers in which PKC activity is inhibited by staurosporine. To further test the function of PKC activity in the regulation of slow MyHC2 expression, wild-type and dominant-negative mutations of PKC alpha and PKC theta were overexpressed in MA muscle fibers in vitro, Overexpression of wild-type PKC alpha and PKC theta cDNAs resulted in increased PKC activities in muscle fibers and concomitant repression of slow MyNC2 expression under conditions that normally induced gene expression. Point mutations leading to single amino acid substitutions were generated in the ATP binding domains of PRC alpha and PKC theta. Overexpression of CMVPKC alpha 368 and CMVPKC theta R409 resulted in decreased PKC activities in transfected MA muscle fibers. Furthermore, transfection of CMVPKC alpha YR368 and CMVPKC theta R409 mutant constructs into RIA muscle fibers did not repress the capacity of these fibers to express slow MyHC2 when cultured in medium containing staurosporine or when innervated. These results indicate that PKC activity represses slow MyHC2 expression and that PKC downregulation, possibly in response to innervation, is required but not sufficient for slow MyHC2 expression. (C) 2001 Academic Press.
引用
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页码:23 / 32
页数:10
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