Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization
Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization
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DOI：
10.1038/383178a0
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发表时间：
1996-09-12
期刊：
影响因子：
64.8
通讯作者：
Perlmutter, RM
中科院分区：
文献类型：
--
作者：
Farrar, MA;AlberolaIla, J;Perlmutter, RM
Raf-1丝氨酸/苏氨酸激酶是MAP激酶级联的关键组分（1-3），调节增殖和细胞命运定型（4，5）。Raf的活化在其易位至质膜后被刺激，这是一个通常需要与膜定位的GTP酶Ras-GTP相互作用的过程（6-10）。为了研究Raf激活的机制，我们开发了一种香豆素诱导的化学二聚化方法。我们发现，二聚化本身是足够的，在没有任何膜组件，既激活一个修改后的Raf蛋白，并适当地刺激MAP激酶级联。由于Ras-GTP诱导的膜定位增加了有效的细胞内Ras浓度，我们的研究结果表明，同型寡聚化通常可以促进Raf在体内的激活。
THE Raf-1 serine/threonine kinase is a key component of the MAP kinase cascade(1-3), regulating both proliferation and commitment to cell fate(4,5). Raf activation is stimulated following its translocation to the plasma membrane, a process that ordinarily requires interaction with the membrane-localized GTPase, Ras-GTP(6-10). To investigate the mechanisms underlying Raf activation, we have developed a coumermycin-induced chemical dimerization method. We find that dimerization is by itself sufficient, in the absence of any membrane components, both to activate a modified Raf protein and to stimulate the MAP kinase cascade appropriately. As Ras-GTP-induced membrane localization increases the effective intracellular Ras concentration, our results indicate that homotypic oligomerization may ordinarily act to promote Raf activation in vivo.