ARIA/HRG regulates AChR epsilon subunit gene expression at the neuromuscular synapse via activation of phosphatidylinositol 3-kinase and Ras/MAPK pathway

被引:115
作者
Tansey, MG
Chu, GC
Merlie, JP
机构
[1] Dept. of Molec. Biol. and Pharmacol., Washington University, School of Medicine, St. Louis
关键词
D O I
10.1083/jcb.134.2.465
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
AChR-inducing activity (ARIA)/heregulin, a ligand for erbB receptor tyrosine kinases (RTKs), is likely to be one nerve-supplied signal that induces expression of acetylcholine receptor (AChR) genes at the developing neuromuscular junction. Since some RTKs act through Ras and phosphatidylinositol 3-kinase (PI3K), we investigated the role of these pathways in ARIA signaling. Expression of activated Ras or Raf mimicked ARIA-induction of AChR epsilon subunit genes in muscle cells; whereas dominant negative Ras or Raf blocked the effect of ARIA, ARIA rapidly activated erk1 and erk2 and inhibition of both erks also abolished the effect of ARIA. ARIA stimulated association of PI3K with erbB3, expression of an activated PI3K led to ARIA-independent AChR epsilon subunit expression, and inhibition of PI3K abolished the action of ARIA. Thus, synaptic induction of AChR genes requires activation of both Ras/MAPK and PI3K signal transduction pathways.
引用
收藏
页码:465 / 476
页数:12
相关论文
共 79 条
[1]   ERBB3 AND ERBB2/NEU MEDIATE THE EFFECT OF HEREGULIN ON ACETYLCHOLINE-RECEPTOR GENE-EXPRESSION IN MUSCLE - DIFFERENTIAL EXPRESSION AT THE END-PLATE [J].
ALTIOK, N ;
BESSEREAU, JL ;
CHANGEUX, JP .
EMBO JOURNAL, 1995, 14 (17) :4258-4266
[2]  
Apel Elizabeth D., 1995, Current Opinion in Neurobiology, V5, P62, DOI 10.1016/0959-4388(95)80088-3
[3]  
Auger K. R., 1990, METHODS INOSITIDE RE, P159
[4]   THE NEU ONCOGENE ENCODES AN EPIDERMAL GROWTH-FACTOR RECEPTOR-RELATED PROTEIN [J].
BARGMANN, CI ;
HUNG, MC ;
WEINBERG, RA .
NATURE, 1986, 319 (6050) :226-230
[5]  
BENBARUCH N, 1994, P SOC EXP BIOL MED, V206, P221
[6]   A SINGLE AUTOPHOSPHORYLATION SITE CONFERS ONCOGENICITY TO THE NEU/ERBB-2 RECEPTOR AND ENABLES COUPLING TO THE MAP KINASE PATHWAY [J].
BENLEVY, R ;
PATERSON, HF ;
MARSHALL, CJ ;
YARDEN, Y .
EMBO JOURNAL, 1994, 13 (14) :3302-3311
[7]   SIGNAL-TRANSDUCTION VIA THE MAP KINASES - PROCEED AT YOUR OWN RSK [J].
BLENIS, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :5889-5892
[8]   IDENTIFICATION OF MULTIPLE EXTRACELLULAR SIGNAL-REGULATED KINASES (ERKS) WITH ANTIPEPTIDE ANTIBODIES [J].
BOULTON, TG ;
COBB, MH .
CELL REGULATION, 1991, 2 (05) :357-371
[9]   SIGNAL-TRANSDUCTION - TEAM BLUE SEES RED [J].
BOURNE, HR .
NATURE, 1995, 376 (6543) :727-729
[10]  
BOWE MA, 1995, ANNU REV NEUROSCI, V18, P443