Apoptosis signal-regulating kinase/nuclear factor-kappaB: a novel signaling pathway regulates cardiomyocyte hypertrophy.
Apoptosis signal-regulating kinase/nuclear factor-kappaB: a novel signaling pathway regulates cardiomyocyte hypertrophy.
复制标题
凋亡信号调节激酶/核因子-kappaB：一种新的信号通路调节心肌细胞肥大。
作者：
T. Force;Syed Haq;H. Kilter;Ashour Michael
自1993年Sadoshima等人发表了他们关于血管紧张素II（Ang II）在牵张诱导的心肌细胞肥大反应中的作用的观察结果以来，我们已经知道肽类激素在细胞牵张刺激的肥大发展、压力超负荷诱导的肥大的起始刺激以及心肌梗死后非梗死心肌中发生的肥大中是重要的。血管紧张素II以及内皮素-1（ET-1）和α-肾上腺素能药物通过结合7种与Gq类异源三聚体G蛋白偶联的跨膜受体激活细胞内途径。这类受体和G蛋白在压力超负荷诱导的肥大中的关键作用由Ahkter等人2优雅地证明，他们表明，小鼠心脏特异性表达一种肽，阻断Gq的信号传递，显著减弱了对主动脉缩窄的肥大反应。
见第509页
在心肌细胞生物学领域占据主导地位的问题是，这些激素如何通过其同源受体和Gq起作用，引发肥大反应？到目前为止，已经得出了一个明确的结论：心肌细胞的肥大反应由相互作用的胞质信号通路的极其复杂的网络调节，3Gq活化最终导致增加胞质游离[Ca 2 +]和活化蛋白激酶C家族成员的中间体的产生，并导致几种蛋白激酶的募集，包括促分裂原活化蛋白激酶（MAPK），钙钙调蛋白依赖性蛋白激酶Akt/PKB和Janus激酶。这些激酶使许多转录因子磷酸化，增加其转录激活活性，并且在某些情况下增加DNA结合活性。升高的[Ca 2 +]还可以激活蛋白磷酸酶，钙调磷酸酶，4使核因子激活的T细胞（NF-AT）转录因子家族的成员去磷酸化，导致其核转位。激活的转录因子与特定的DNA序列结合...
Since 1993, when Sadoshima et al1 published their observations on the role of Angiotensin II (Ang II) in the stretch-induced hypertrophic response of cardiomyocytes, we have known that peptide hormones were important in the development of hypertrophy stimulated by cell stretch, the initiating stimulus in pressure overload-induced hypertrophy and in the hypertrophy that occurs in the noninfarcted myocardium following a myocardial infarction. Ang II, as well as endothelin-1 (ET-1) and α-adrenergic agents, activate intracellular pathways by binding to 7 transmembrane-spanning receptors coupled to heterotrimeric G proteins of the Gq class. The critical role of this class of receptors and G proteins in pressure overload-induced hypertrophy was elegantly demonstrated by Ahkter et al2 who showed that cardiac specific expression in mice of a peptide that blocked signal transmission by Gq markedly blunted the hypertrophic response to aortic banding.
See p 509
The question that has dominated the field of cardiomyocyte biology is how do these hormones, acting via their cognate receptors and Gq, trigger the hypertrophic response? One clear conclusion has evolved thus far: the hypertrophic response of cardiomyocytes is regulated by an enormously complex network of interacting cytosolic signaling pathways.3 Gq activation ultimately results in the production of intermediates that increase cytosolic free [Ca2+] and activate members of the protein kinase C family, and leads to the recruitment of several protein kinases, including the mitogen-activated protein kinases (MAPKs), calcium calmodulin-dependent protein kinases, Akt/PKB, and the Janus kinases. These kinases phosphorylate a number of transcription factors, increasing their transcriptional activating activity and, in some cases, DNA binding activity. Elevated [Ca2+] can also activate the protein phosphatase, calcineurin,4 which dephosphorylates members of the nuclear factor-activated T cell (NF-AT) family of transcription factors, causing their nuclear translocation. Activated transcription factors bind to specific DNA sequences …
影响因子：
15.9
作者：
Choukroun, G;Hajjar, R;Force, T
通讯作者：
Force, T
影响因子：
15.9
作者：
Liang, FQ;Gardner, DG
通讯作者：
Gardner, DG
影响因子：
56.9
作者：
Akhter, SA;Luttrell, LM;Koch, WJ
通讯作者：
Koch, WJ