title: Electrical activity regulates AChR gene expression via JNK, PKCzeta and Sp1 in skeletal chick muscle.
abstract: 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.
authors.affiliation: Kadir Has University Medical Faculty, Department of Pharmacology, Istanbul, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Altiok
authors.forename: J P
authors.initials: JP
authors.lastname: Changeux
mesh_terms: 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
chemical_list: 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