监管和角色Raf-1 / b - raf heterodimerization。
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拉什沃斯路,欣德利广告,奥尼尔E, Kolch W
监管和角色Raf-1 / b - raf heterodimerization。
摩尔细胞杂志。2006年3月,26 (6):2262 - 72。
- PubMed ID
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16508002 (在PubMed]
- 文摘
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的Ras-Raf-MEK-extracellular signal-regulated激酶(ERK)的控制通路参与许多基本的细胞过程包括增殖、存活和分化。通路是管制在多达30%的人类癌症,经常由于Ras突变和b - raf同种型。Raf-1和b - raf可以形成形成,这可能是重要的细胞转变。在这里,我们分析了Raf-1 / b - raf的生化和生物性质形成。孤立Raf-1 / b - raf形成具有高度增加激酶活性相比,各自为或单体。野生型Raf-1和b - raf突变体之间形成较低或没有激酶活性仍然显示激酶活性升高,野生型之间形成b - raf和kinase-negative Raf-1。相比之下,形成包含kinase-negative Raf-1 kinase-negative b - Raf完全不活跃,表明异质二聚体的激酶活性特别是源于英国皇家空军,要么kinase-competent Raf同种型足以赋予高催化活性的异质二聚体。在细胞系,Raf-1 / b - raf形成被发现在低水平。Heterodimerization增强了14-3-3蛋白独立于ERK和有丝分裂原。然而,ERK-induced磷酸化的b - Raf T753促进了英国皇家空军的拆卸,形成的突变T753长期增长因素heterodimerization。 The B-Raf T753A mutant enhanced differentiation of PC12 cells, which was previously shown to be dependent on sustained ERK signaling. Fine mapping of the interaction sites by peptide arrays suggested a complex mode of interaction involving multiple contact sites with a main Raf-1 binding site in B-Raf encompassing T753. In summary, our data suggest that Raf-1/B-Raf heterodimerization occurs as part of the physiological activation process and that the heterodimer has distinct biochemical properties that may be important for the regulation of some biological processes.