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J. Biol. Chem., Vol. 269, Issue 45, 27811-27814, 11, 1994
MK Sapru, G Zhou and D Goldman
Innervation of skeletal muscles results in expression of adult-type
nicotinic acetylcholine receptors (alpha 2 beta epsilon delta) beneath the
neuromuscular junction. This local expression is largely a result of
selective induction of adult-type nicotinic acetylcholine receptor (nAChR)
genes in endplate-associated myonuclei. The molecular mechanism by which
the nerve induces gene expression in these nuclei is not known. We have
shown previously that ionophore-induced calcium influx across the plasma
membrane preferentially decreases expression from the adult-type specific
nAChR epsilon-subunit gene (Walke, W., Staple, J., Adams, L., Gnegy, M.,
Chahine, K., and Goldman, D. (1994) J. Biol. Chem. 269, 19447-19456). Here
we provide evidence that the genes encoding adult-type nAChRs are
specifically regulated by protein- tyrosine phosphatase activity.
Orthovanadate, a specific protein- tyrosine phosphatase inhibitor, caused
increased expression of the epsilon-subunit gene in rat primary myotubes
and was able to completely block the suppressive effects of increased
calcium influx on epsilon- subunit RNA expression. Overexpression of
protein-tyrosine phosphatases selectively decreased expression from the
adult-type nAChR genes with no effect on the embryonic-type specific
gamma-subunit gene. These results demonstrate that protein-tyrosine
phosphatases regulate mammalian adult-type nAChR gene expression and
suggest a mechanism by which muscle innervation selectively regulates gene
expression in endplate-associated myonuclei.
Protein-tyrosine phosphatases specifically regulate muscle adult-type nicotinic acetylcholine receptor gene expression
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
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