PMID: 9448324Mar 14, 1998Paper

Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor

Proceedings of the National Academy of Sciences of the United States of America
M K SapruD Goldman

Abstract

At the neuromuscular synapse, innervation induces endplate-specific expression of adult-type nicotinic acetylcholine receptors by selective expression of their subunit-encoding genes (alpha2betaepsilondelta) in endplate-associated myonuclei. These genes are specifically regulated by protein-tyrosine phosphatase (PTPase) activity. In addition, neuregulin/acetylcholine-receptor-inducing activity, a nerve-derived factor that stimulates nicotinic acetylcholine receptor synthesis, induces adult-type specific epsilon subunit gene expression via activation of a Ras/mitogen-activated protein kinase pathway. However, the DNA regulatory elements and the binding proteins that mediate PTPase and neuregulin-dependent gene expression remain unknown. Herein we report that PTPase, neuregulin, and Ras-dependent regulation of the epsilon subunit gene map to a 15-bp promoter sequence. Interestingly, this same 15-bp sequence appears to be necessary for low epsilon subunit gene expression in extrajunctional regions of the muscle fiber. Site-directed mutagenesis of a putative Ets binding site located within this 15-bp sequence, reduced PTPase, neuregulin, and Ras-dependent regulation. Overexpression of the rat muscle Ets-2 transcription factor resul...Continue Reading

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Citations

Apr 15, 1999·Annual Review of Neuroscience·J R Sanes, J W Lichtman
Feb 15, 2001·Oncogene·V I Sementchenko, D K Watson
Jan 1, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Joe V Chakkalakal, Bernard J Jasmin
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