Phosphorylation of Elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy

被引:74
作者
Babu, GJ
Lalli, MJ
Sussman, MA
Sadoshima, J
Periasamy, M [1 ]
机构
[1] Univ Cincinnati, Coll Med, Dept Internal Med, Div Cardiol,Lab Mol Cardiol, Cincinnati, OH 45267 USA
[2] Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH 45267 USA
[3] Penn State Univ, Coll Med, Weis Ctr Res, Danville, PA 17822 USA
关键词
cardiac hypertrophy; c-fos; Elk-1; MEK; ERK; phenylephrine; SRE;
D O I
10.1006/jmcc.2000.1185
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cardiac hypertrophy is associated with specific alterations in myocardial gene expression; however, the exact mechanisms responsible for altered gene expression are poorly defined. The goal of this study was to investigate whether signaling kinases that are activated during cardiac hypertrophy directly modulate transcription factor activity and regulate gene expression. In an effort to understand this process, we focused our studies on the transcriptional activation of c-fos gene through the serum response element (SRE)/ternary complex factor (TCF) element, during phenylephrine-induced myocyte hypertrophy. In this study, we show that phosphorylated Elk-1, a TCE binds to c-fos SRE and its binding to SRE is increased upon phenylephrine stimulation. Phenylephrine treatment activates phosphorylation of Elk-1 in the nucleus within five minutes and Elk-1-dependent transcriptional activation is abolished by inhibitors selective for MEK/ERK kinases. These studies implicate that phosphorylation of Elk-1 by ERK kinase pathway is important for early gene activation during phenylephrine-induced myocyte hypertrophy. (C) 2000 Academic Press.
引用
收藏
页码:1447 / 1457
页数:11
相关论文
共 29 条
[1]  
AOYAGI T, 1993, J BIOL CHEM, V268, P27176
[2]   EFFECT OF THYROID-HORMONE ON THE EXPRESSION OF MESSENGER-RNA ENCODING SARCOPLASMIC-RETICULUM PROTEINS [J].
ARAI, M ;
OTSU, K ;
MACLENNAN, DH ;
ALPERT, NR ;
PERIASAMY, M .
CIRCULATION RESEARCH, 1991, 69 (02) :266-276
[3]  
BISHOPRIC NH, 1992, J BIOL CHEM, V267, P25535
[4]   Adrenergic receptor stimulation of the mitogen-activated protein kinase cascade and cardiac hypertrophy [J].
Bogoyevitch, MA ;
Andersson, MB ;
GillespieBrown, J ;
Clerk, A ;
Glennon, PE ;
Fuller, SJ ;
Sugden, PH .
BIOCHEMICAL JOURNAL, 1996, 314 :115-121
[5]   Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry [J].
Brunet, A ;
Roux, D ;
Lenormand, P ;
Dowd, S ;
Keyse, S ;
Pouysségur, J .
EMBO JOURNAL, 1999, 18 (03) :664-674
[6]   TRANSCRIPTIONAL REGULATION DURING CARDIAC GROWTH AND DEVELOPMENT [J].
CHIEN, KR ;
ZHU, H ;
KNOWLTON, KU ;
MILLERHANCE, W ;
VANBILSEN, M ;
OBRIEN, TX ;
EVANS, SM .
ANNUAL REVIEW OF PHYSIOLOGY, 1993, 55 :77-95
[7]   Angiotensin II type(1a) receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload [J].
Herzig, TC ;
Jobe, SM ;
Aoki, H ;
Molkentin, JD ;
Cowley, AW ;
Izumo, S ;
Markham, BE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) :7543-7548
[8]   Growth hormone stimulates phosphorylation and activation of Elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2 [J].
Hodge, C ;
Liao, JF ;
Stofega, M ;
Guan, KL ;
Carter-Su, C ;
Schwartz, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (47) :31327-31336
[9]   PROTOONCOGENE INDUCTION AND REPROGRAMMING OF CARDIAC GENE-EXPRESSION PRODUCED BY PRESSURE OVERLOAD [J].
IZUMO, S ;
NADALGINARD, B ;
MAHDAVI, V .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (02) :339-343
[10]   Growth hormone regulates ternary complex factors and serum response factor associated with the c-fos serum response element [J].
Liao, JF ;
Hodge, C ;
Meyer, D ;
Ho, PS ;
Rosenspire, K ;
Schwartz, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (41) :25951-25958