Electrical activity regulates AChR gene expression via JNK, PKCzeta and Sp1 in skeletal chick muscle.
Electrical activity of myotubes represses nicotinic acetylcholine receptor (AChR) gene expression. This effect is mimicked by okadaic acid and blocked by tetrodotoxin (TTX) or staurosporine in cultured myocytes [Altiok et al., EMBO J. 16 (1997) 717-725]. In this study, we investigated the mechanism of this repression. We show that addition of exogenous phospholipase D (PLD) and C inhibits AChR expression in a manner which parallels that of okadaic acid. Furthermore, okadaic acid caused an increase of the threonine phosphorylation of protein kinase Czeta (PKCzeta) and activator of transcription factor (ATF2) and a decrease of the phosphorylation of Sp1. All these effects were reversed by staurosporine, and TTX also abolished ATF2 phosphorylation. These data reveal a possible involvement of PLD, c-jun N-terminal kinase, PKCzeta and Sp1 in the repression of AChR genes by electrical activity.
Altiok
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Kadir Has University Medical Faculty, Department of Pharmacology, Istanbul, Turkey.
Changeux
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JP
D051698:Activating Transcription Factor 2; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics*; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D000099221:Protein Kinase C zeta
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019319:Okadaic Acid; D011493:Protein Kinase C; D011978:Receptors, Nicotinic; D016329:Sp1 Transcription Factor; D019311:Staurosporine; D013779:Tetrodotoxin; D014157:Transcription Factors; D000099221:Protein Kinase C zeta