Linked Life Data

17185343

Source:http://linkedlifedata.com/resource/pubmed/id/17185343

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pubmed-article:17185343pubmed:abstractTextThe transcription factor nuclear factor of activated T cells (NFAT)c1 has been shown to be involved in turning on slow skeletal muscle fibre gene expression. Previous studies from our laboratory have characterized the stimulation pattern-dependent nuclear import and resting shuttling of NFATc1-green fluorescent protein (GFP) in flexor digitorum brevis (FDB) muscle fibres from adult mouse. In this study, we use viral expression of the transcription factor NFATc1-GFP fusion protein to investigate the mechanisms underlying the nuclear export of the NFATc1-GFP that accumulated in the nuclei of cultured dissociated adult mouse FDB muscle fibres during slow-twitch fibre type electrical stimulation. In these studies, we found that inhibition of either glycogen synthase kinase 3beta (GSK3beta) or casein kinase 1 or 2 (CK1/2) markedly slowed the decay of nuclear NFATc1-GFP after cessation of muscle fibre electrical stimulation, whereas inhibition of casein kinase 1delta, p38 mitogen-activated protein kinase, c-Jun N-terminal kinase and protein kinase A had little effect. Simultaneous inhibition of GSK3beta and CK1/2 completely blocked the nuclear export of NFATc1-GFP after muscle activity. We also developed a simplified model of NFATc1 phosphorylation/dephosphorylation and nuclear fluxes, and used this model to simulate the observed time courses of nuclear NFATc1-GFP with and without NFATc1 kinase inhibition. Our results suggest that GSK3beta and CK1/2 are the major protein kinases that contribute to the removal of NFATc1 that accumulates in muscle fibre nuclei during muscle activity, and that GSK3beta and CK1/2 are responsible for phosphorylating NFATc1 in muscle nuclei in a complementary or synergistic fashion.lld:pubmed
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pubmed-article:17185343pubmed:issn0022-3751lld:pubmed
pubmed-article:17185343pubmed:authorpubmed-author:SchneiderMart...lld:pubmed
pubmed-article:17185343pubmed:authorpubmed-author:ShenTiansheng...lld:pubmed
pubmed-article:17185343pubmed:authorpubmed-author:RandallWillia...lld:pubmed
pubmed-article:17185343pubmed:authorpubmed-author:CseresnyésZol...lld:pubmed
pubmed-article:17185343pubmed:authorpubmed-author:LiuYeweiYlld:pubmed
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pubmed-article:17185343pubmed:dateRevised2011-11-2lld:pubmed
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