Phosphorylation of Elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy
Phosphorylation of Elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy
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DOI：
10.1006/jmcc.2000.1185
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发表时间：
2000-08-01
影响因子：
5
通讯作者：
Periasamy, M
中科院分区：
文献类型：
--
作者：
Babu, GJ;Lalli, MJ;Periasamy, M
心脏肥大与心肌基因表达的特定改变有关；然而，导致基因表达改变的确切机制尚不清楚。本研究的目的是调查心脏肥大期间激活的信号激酶是否直接调节转录因子活性并调节基因表达。为了理解这一过程，我们将研究重点放在去氧肾上腺素诱导的肌细胞肥大期间，通过血清反应元件（SRE）/三元复合因子（TCF）元件对c-fos基因的转录激活。在这项研究中，我们发现磷酸化的 Elk-1（一种 TCE）与 c-fos SRE 结合，并且在去氧肾上腺素刺激下，其与 SRE 的结合增加。去氧肾上腺素处理可在五分钟内激活细胞核中 Elk-1 的磷酸化，并且对 MEK/ERK 激酶具有选择性的抑制剂可消除 Elk-1 依赖性转录激活。这些研究表明，ERK 激酶途径对 Elk-1 的磷酸化对于去氧肾上腺素诱导的肌细胞肥大期间的早期基因激活非常重要。 (C) 2000 年学术出版社。
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.