Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization

被引:272
作者
Farrar, MA
AlberolaIla, J
Perlmutter, RM
机构
[1] UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195
[2] UNIV WASHINGTON,DEPT BIOCHEM & MED MED GENET,SEATTLE,WA 98195
[3] UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195
关键词
D O I
10.1038/383178a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:178 / 181
页数:4
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