TY - JOUR
T1 - Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase
AU - Si, Jutong
AU - Luo, Zhijun
AU - Lin, Mei
PY - 1996
Y1 - 1996
N2 - Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits (α, β, γ or ε, and δ) is highest in nuclei localized to the synaptic region of the muscle, which contributes to maintain a high density of AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in the subsynaptic area. To elucidate the signaling mechanism initiated by ARIA, we established stable C2C12 cell lines carrying the nuclear lacZ gene under the control of the mouse ε subunit promoter or chicken α subunit promoter. ARIA stimulated tyrosine phosphorylation of erbB proteins in these C2C12 cells within 15s with a peak at 5 min. Immediately following tyrosine phosphorylation of erbB proteins, mitogen-activated protein (MAP) kinase was activated which occurred within 30 s and peaked at 8 min after ARIA stimulation. Concomitantly, expression of AChR genes was induced by ARIA. ARIA-induced AChR subunit transgene expression was observed only in differentiated myotubes and not in myoblasts, suggesting that downstream signaling component(s) are regulated in a manner dependent on the myogenic program. Inhibition of the MAP kinase activity by using a specific MAP kinase inhibitor or by overexpressing dominant negative mutants of Raf or MAP kinase attenuated or abolished the ARIA-induced activation of AChR α and subunit gene expression. These results indicate that regulation of AChR gene expression by ARIA in C2C12 cells requires activation of the MAP kinase signaling pathway.
AB - Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits (α, β, γ or ε, and δ) is highest in nuclei localized to the synaptic region of the muscle, which contributes to maintain a high density of AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in the subsynaptic area. To elucidate the signaling mechanism initiated by ARIA, we established stable C2C12 cell lines carrying the nuclear lacZ gene under the control of the mouse ε subunit promoter or chicken α subunit promoter. ARIA stimulated tyrosine phosphorylation of erbB proteins in these C2C12 cells within 15s with a peak at 5 min. Immediately following tyrosine phosphorylation of erbB proteins, mitogen-activated protein (MAP) kinase was activated which occurred within 30 s and peaked at 8 min after ARIA stimulation. Concomitantly, expression of AChR genes was induced by ARIA. ARIA-induced AChR subunit transgene expression was observed only in differentiated myotubes and not in myoblasts, suggesting that downstream signaling component(s) are regulated in a manner dependent on the myogenic program. Inhibition of the MAP kinase activity by using a specific MAP kinase inhibitor or by overexpressing dominant negative mutants of Raf or MAP kinase attenuated or abolished the ARIA-induced activation of AChR α and subunit gene expression. These results indicate that regulation of AChR gene expression by ARIA in C2C12 cells requires activation of the MAP kinase signaling pathway.
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U2 - 10.1074/jbc.271.33.19752
DO - 10.1074/jbc.271.33.19752
M3 - Article
C2 - 8702681
AN - SCOPUS:0029786737
SN - 0021-9258
VL - 271
SP - 19752
EP - 19759
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 33
ER -