PH domain of ELMO functions in trans to regulate Rac activation via Dock180

作者: Mingjian Lu , Jason M Kinchen , Kent L Rossman , Cynthia Grimsley , Colin deBakker

DOI: 10.1038/NSMB800

关键词:

摘要: The members of the Dock180 superfamily proteins are novel guanine nucleotide exchange factors (GEF) for Rho family GTPases and linked to multiple biological processes from worms mammals. ELMO is a critical regulator Dock180, Dock180-ELMO complex functions as bipartite GEF Rac. We identified mechanism wherein PH domain ELMO, by binding Dock180-Rac in trans, stabilizes Rac nucleotide-free transition state. Mutagenesis studies reveal that this domain-dependent regulation essential function phagocytosis cell migration. Genetic rescue Caenorhabditis elegans using its homolog CED-12 support above observations vivo. These data new mode action domains novel, evolutionarily conserved which can activate

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