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首页> 外文期刊>Molecular and Cellular Biology >The Molecular Scaffold KSR1 Regulates the Proliferative and Oncogenic Potential of Cells
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The Molecular Scaffold KSR1 Regulates the Proliferative and Oncogenic Potential of Cells

机译：分子支架KSR1调节细胞的增殖和致癌潜能。

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The specificity of signaling through mitogen-activated protein kinase pathways has been attributed to both the control of intensity and duration of signaling and the actions of protein scaffolds. Here we demonstrate that the molecular scaffold KSR1 regulates the intensity and duration of ERK activation to modulate a cell's proliferative and oncogenic potential. Deletion of KSR1 eliminates the prolonged phase of ERK activation induced by platelet-derived growth factor and blocks RasV12-induced transformation. The introduction of KSR1 into KSR1?/? mouse embryo fibroblasts causes a concentration-dependent increase in signaling and transformation, to a maximum at 14 times the wild-type KSR1 expression levels, but inhibits these responses at higher expression levels. An increase in KSR1 expression to levels that are optimal for signaling leads to a threefold increase in proliferative capacity and is coincident with the level of KSR1 expression that maximally associates with all members of the Raf/MEK/ERK cascade. These data reveal that cells contain a reserve proliferative capacity that is accessible by the optimal expression of a noncatalytic signaling component and that altering the expression level of a molecular scaffold can modulate the actions of growth factors and oncogenes.
机译：通过促分裂原活化的蛋白激酶途径的信号转导的特异性已被归因于信号强度和持续时间的控制以及蛋白质支架的作用。在这里，我们证明了分子支架KSR1调节ERK激活的强度和持续时间，以调节细胞的增殖和致癌潜力。删除KSR1可消除血小板衍生的生长因子诱导的ERK活化的延长阶段，并阻止Ras V12 诱导的转化。将KSR1引入KSR1 ？/？小鼠胚胎成纤维细胞会引起信号传导和转化的浓度依赖性增加，最大达到野生型KSR1表达水平的14倍，但在更高的水平抑制这些反应表达水平。 KSR1表达增加至最适合信号转导的水平，导致增殖能力增加三倍，并且与最大程度地与Raf / MEK / ERK级联的所有成员相关的KSR1表达水平一致。这些数据表明，细胞具有储备增殖能力，可以通过非催化信号组分的最佳表达来获得，并且改变分子支架的表达水平可以调节生长因子和癌基因的作用。

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