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Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor.

机译:表皮生长因子(EGF)刺激Raf-1与EGF受体的缔合和激酶活性。

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Raf-1 serine- and threonine-specific protein kinase is transiently activated in cells expressing the epidermal growth factor (EGF) receptor upon treatment with EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and mediates protein kinase C-independent phosphorylation of Raf-1 on serine residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate gels and has sixfold-increased activity in immunocomplex kinase assay with histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity in inactive in Raf-1 coupling and association. It is noteworthy that tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these cells. These observations suggest that Raf-1 kinase may act as an important downstream effector of EGF signal transduction.
机译:用表皮生长因子(EGF)处理后,Raf-1丝氨酸和苏氨酸特异性蛋白激酶在表达表皮生长因子(EGF)受体的细胞中被瞬时激活。刺激的EGF受体与Raf-1激酶共免疫沉淀,并介导丝氨酸残基上Raf-1的蛋白激酶C依赖性磷酸化。高磷酸化的Raf-1在十二烷基硫酸钠凝胶上的迁移率较低,并且在以组蛋白H1或Raf-1序列衍生的肽为底物的免疫复合激酶测定中,其活性增加了六倍。 Raf-1激活需要激酶活性EGF受体;缺乏酪氨酸激酶活性的点突变体,在Raf-1偶联和缔合中无效。值得注意的是,在这些细胞中未检测到由EGF诱导的c-Raf-1的酪氨酸磷酸化。这些观察结果表明,Raf-1激酶可能是EGF信号转导的重要下游效应子。

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