Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase

Jutong Si, Zhijun Luo, Lin Mei

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19752-19759
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number33
DOIs
StatePublished - Sep 5 1996

Fingerprint

Cholinergic Receptors
Mitogen-Activated Protein Kinases
Gene expression
Chemical activation
Gene Expression
Phosphorylation
Tyrosine
Genes
Gene encoding
Lac Operon
Myoblasts
Skeletal Muscle Fibers
Nicotinic Receptors
Motor Neurons
Transcription
Protein Kinase Inhibitors
Transgenes
Neurons
Muscle
Chickens

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase. / Si, Jutong; Luo, Zhijun; Mei, Lin.

In: Journal of Biological Chemistry, Vol. 271, No. 33, 05.09.1996, p. 19752-19759.

Research output: Contribution to journalArticle

@article{cdcbae8a2b6141db93befc985918bbc5,
title = "Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase",
abstract = "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.",
author = "Jutong Si and Zhijun Luo and Lin Mei",
year = "1996",
month = "9",
day = "5",
doi = "10.1074/jbc.271.33.19752",
language = "English (US)",
volume = "271",
pages = "19752--19759",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "33",

}

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 - Mei, Lin

PY - 1996/9/5

Y1 - 1996/9/5

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.

UR - http://www.scopus.com/inward/record.url?scp=0029786737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029786737&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.33.19752

DO - 10.1074/jbc.271.33.19752

M3 - Article

VL - 271

SP - 19752

EP - 19759

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 33

ER -