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首页> 外文期刊>Molecular and Cellular Biology >p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels
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p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels

机译：p38α异构体Mxi2与细胞外信号调节激酶1和2丝裂原激活的蛋白激酶结合，并通过维持其磷酸化水平来调节其核活性。

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摘要

Mxi2 is a p38α splice isoform that is distinctively activated by mitogenic stimuli. Here we show that Mxi2 immunoprecipitates carry a kinase activity that is persistently activated by epidermal growth factor in a fashion regulated by Ras, Raf, and MEK. We demonstrate that this kinase activity can be attributed not to Mxi2 but rather to extracellular signal-regulated kinases 1 and 2 (ERK1/2), which coimmunoprecipitated with Mxi2 both by ectopic expression and in a physiological environment like the kidney. Furthermore, we provide evidence that Mxi2-ERK interaction has profound effects on ERK function, demonstrating that Mxi2 prolongs the duration of the ERK signal by sustaining its phosphorylation levels. Interestingly, we show that the effects of Mxi2 on ERK are restricted to nuclear events. Mxi2 potently up-regulates ERK-mediated activation of the transcription factors Elk1 and HIF1α but has no effect on the activity of ERK cytoplasmic substrates RSK2 and cPLA2, induced by epidermal growth factor or by MEK. Overall, our findings point to Mxi2 as a unique member of the p38 family that may have an unprecedented role in the regulation of the functions of ERK mitogen-activated protein kinases.
机译：Mxi2是p38α剪接同工型，由有丝分裂刺激明显激活。在这里，我们显示Mxi2免疫沉淀物具有被Ras，Raf和MEK调节的方式被表皮生长因子持续激活的激酶活性。我们证明这种激酶活性可以不归因于Mxi2，而是归因于细胞外信号调节激酶1和2（ERK1 / 2），其通过异位表达和在诸如肾脏的生理环境中与Mxi2共免疫沉淀。此外，我们提供的证据表明Mxi2-ERK相互作用对ERK功能具有深远的影响，表明Mxi2通过维持其磷酸化水平来延长ERK信号的持续时间。有趣的是，我们表明Mxi2对ERK的作用仅限于核事件。 Mxi2可能上调ERK介导的转录因子Elk1和HIF1α的激活，但对表皮生长因子或MEK诱导的ERK细胞质底物RSK2和cPLA 2 的活性没有影响。总体而言，我们的发现表明Mxi2是p38家族的独特成员，它可能在ERK促有丝分裂原活化蛋白激酶功能的调节中发挥着前所未有的作用。

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