Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy.
Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy.
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DOI：
10.1111/j.1749-6632.2009.05088.x
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发表时间：
2010-03
影响因子：
5.2
通讯作者：
Molkentin JD
中科院分区：
文献类型：
--
作者：
Kehat I;Molkentin JD
心脏肥大是由于心脏机械负荷增加和神经-体液介质的作用所致。已知ERK1/2在几乎所有应激和激动剂诱导的肥厚刺激下都被激活，这表明这些激酶是促进心脏生长反应所必需的直接假设。然而，最近来自转基因小鼠模型的数据显示了一个更为复杂的图景。例如，诱导表达双特异性磷酸酶6，一种ERK1/2灭活磷酸酶，消除了转基因小鼠中ERK1/2的磷酸化，但它并没有减少对压力过载的肥厚反应。同样，Erk1−/−和Erk2+/−小鼠体内刺激诱导的心脏生长没有减少。然而，阻断或缺失心脏ERK1/2确实易使心脏在长期压力过载后失代偿和衰竭。因此，ERK1/2信号并非介导心肌肥厚的绝对必要条件，尽管它在应激刺激过程中确实提供了关键的保护作用/信号。
Cardiac hypertrophy results from increased mechanical load on the heart and through the action of neuro-humoral mediators. ERK1/2 are known to be activated in response to almost every stress- and agonist-induced hypertrophic stimulus examined to date, suggesting the straightforward hypothesis that these kinases are required for promoting the cardiac growth response. However, recent data from genetically modified mouse models suggest a more complicated picture. For example, inducible expression of dual-specificity phosphatase 6, an ERK1/2-inactivating phosphatase, eliminated ERK1/2 phosphorylation in transgenic mice, but it did not diminish the hypertrophic response to pressure overload. Similarly, Erk1−/− and Erk2+/− mice showed no reduction in stimulus-induced cardiac growth in vivo. However, blockade or deletion of cardiac ERK1/2 did predispose the heart to decompensation and failure after long-term pressure overload. Thus, ERK1/2 signaling is not to be absolutely necessary for mediating cardiac hypertrophy, although it does appear to provide critical protective effects/signals during stress-stimulation.
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影响因子：
11.4
作者：
Bueno, OF;De Windt, LJ;Molkentin, JD
通讯作者：
Molkentin, JD
DOI：
10.1016/0735-1097(93)90455-a
发表时间：
1993-10-01
影响因子：
24
作者：
HO, KKL;PINSKY, JL;LEVY, D
通讯作者：
LEVY, D
影响因子：
56.9
作者：
LANGECARTER, CA;PLEIMAN, CM;JOHNSON, GL
通讯作者：
JOHNSON, GL
DOI：
10.1083/jcb.148.5.849
发表时间：
2000-03-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Adachi M;Fukuda M;Nishida E
通讯作者：
Nishida E
影响因子：
5.3
作者：
Liang, QR;Wiese, RJ;Molkentin, JD
通讯作者：
Molkentin, JD