Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex
Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex
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DOI：
10.1038/ncb824
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发表时间：
2002-08-01
影响因子：
21.3
通讯作者：
Ravichandran, KS
中科院分区：
文献类型：
--
作者：
Brugnera, E;Haney, L;Ravichandran, KS
哺乳动物Dock 180和埃尔莫蛋白以及它们在秀丽隐杆线虫和黑腹果蝇中的同源物在发育和细胞迁移过程中作为Rac的关键上游调节剂起作用。Dock 180或埃尔莫介导Rac激活的机制尚不清楚。在这里，我们确定了Dock 180（表示Docker）内的一个结构域，它特异性识别无核苷酸的Rac，并可以在体外介导GTP加载Rac。Docker结构域在后生动物和酵母蛋白中的已知Dock 180家族成员中是保守的。在细胞中，Dock 180与Rac单独结合不足以负载GTP，需要Dock 180-ELMO 1相互作用。我们还可以检测到三聚体ELMO 1-Dock 180-Rac 1复合物，并且埃尔莫增强了Dock 180和Rac之间的相互作用。我们建议，码头180-埃尔莫复杂的功能作为一个非常规的两部分交换因子的RAC。
Mammalian Dock180 and ELMO proteins, and their homologues in Caenorhabditis elegans and Drosophila melanogaster, function as critical upstream regulators of Rac during development and cell migration. The mechanism by which Dock180 or ELMO mediates Rac activation is not understood. Here, we identify a domain within Dock180 (denoted Docker) that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro. The Docker domain is conserved among known Dock180 family members in metazoans and in a yeast protein. In cells, binding of Dock180 to Rac alone is insufficient for GTP loading, and a Dock180-ELMO1 interaction is required. We can also detect a trimeric ELMO1-Dock180-Rac1 complex and ELMO augments the interaction between Dock180 and Rac. We propose that the Dock180-ELMO complex functions as an unconventional two-part exchange factor for Rac.