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首页> 外文期刊>Molecular and Cellular Biology >Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy
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Deletion of Ribosomal S6 Kinases Does Not Attenuate Pathological, Physiological, or Insulin-Like Growth Factor 1 Receptor-Phosphoinositide 3-Kinase-Induced Cardiac Hypertrophy

机译：核糖体S6激酶的删除不会减弱病理，生理或胰岛素样生长因子1受体磷酸肌醇3-激酶诱导的心肌肥大。

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Ribosomal S6 kinases (S6Ks) have been depicted as critical effectors downstream of growth factor pathways, which play an important role in the regulation of protein synthesis by phosphorylating the ribosomal protein, S6. The goal of this study was to determine whether S6Ks regulate heart size, are critical for the induction of cardiac hypertrophy in response to a pathological or physiological stimulus, and whether S6Ks are critical downstream effectors of the insulin-like growth factor 1 (IGF1)-phosphoinositide 3-kinase (PI3K) pathway. For this purpose, we generated and characterized cardiac-specific S6K1 and S6K2 transgenic mice and subjected S6K1?/?, S6K2?/?, and S6K1?/? S6K2?/? mice to a pathological stress (aortic banding) or a physiological stress (exercise training). To determine the genetic relationship between S6Ks and the IGF1-PI3K pathway, S6K transgenic and knockout mice were crossed with cardiac-specific transgenic mice overexpressing the IGF1 receptor (IGF1R) or PI3K mutants. Here we show that overexpression of S6K1 induced a modest degree of hypertrophy, whereas overexpression of S6K2 resulted in no obvious cardiac phenotype. Unexpectedly, deletion of S6K1 and S6K2 had no impact on the development of pathological, physiological, or IGF1R-PI3K-induced cardiac hypertrophy. These studies suggest that S6Ks alone are not essential for the development of cardiac hypertrophy.
机译：核糖体S6激酶（S6Ks）已被描述为生长因子途径下游的关键效应子，它们通过使核糖体蛋白S6磷酸化而在蛋白质合成的调节中发挥重要作用。这项研究的目的是确定S6Ks是否调节心脏大小，对于响应病理性或生理刺激引起的心肌肥大至关重要，以及S6Ks是否是胰岛素样生长因子1（IGF1）的关键下游效应子-磷酸肌醇3激酶（PI3K）途径。为此，我们生成并鉴定了心脏特异性S6K1和S6K2转基因小鼠，并对其进行了S6K1 ？/？，S6K2 ？/？和S6K1 ？/？的处理。 S6K2 ？/？小鼠遭受病理应激（主动脉束带）或生理应激（运动训练）。为了确定S6K和IGF1-PI3K途径之间的遗传关系，将S6K转基因和基因敲除小鼠与过度表达IGF1受体（IGF1R）或PI3K突变体的心脏特异性转基因小鼠杂交。在这里，我们显示S6K1的过表达诱导了一定程度的肥大，而S6K2的过表达则没有明显的心脏表型。出乎意料的是，S6K1和S6K2的删除对病理性，生理性或IGF1R-PI3K诱导的心脏肥大的发展没有影响。这些研究表明，单独的S6K对心脏肥大的发展不是必不可少的。

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