Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex

@article{Brugnera2002UnconventionalRA,
  title={Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex},
  author={Enrico Brugnera and Lisa B. Haney and Cynthia M. Grimsley and Mingjian Lu and Scott F. Walk and Annie-Carole Tosello-Trampont and Ian G. Macara and Hiten D. Madhani and Gerald R. Fink and Kodi S. Ravichandran},
  journal={Nature Cell Biology},
  year={2002},
  volume={4},
  pages={574-582}
}
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… 

Figures from this paper

PH domain of ELMO functions in trans to regulate Rac activation via Dock180
TLDR
This work has identified a mechanism wherein the PH domain of ELMO, by binding the Dock180–Rac complex in trans, stabilizes Rac in the nucleotide-free transition state and reveals a new mode of action of PH domains.
Dock180 and ELMO1 Proteins Cooperate to Promote Evolutionarily Conserved Rac-dependent Cell Migration*
TLDR
This finding suggests that Rac activation by the ELMO·Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.
Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity
TLDR
A novel protein domain is identified named DHR-2 (Dock Homology Region-2) that specifically binds to nucleotide-free Rac and activates Rac in vitro and in vivo and is suggested to be an evolutionarily conserved DOCK180-related superfamily of exchange factors.
Determining the differential roles of the Dock family of GEFs in Drosophila development
TLDR
The roles of Spg and Mbc are not redundant in the Drosophila somatic muscle, central nervous system (CNS), or the dorsal vessel and it is shown that Mbc and Spg can have differential downstream GTPase targets.
Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex
TLDR
Cryo–electron microscopy structure and mutagenesis of the ELMO1-DOCK5 complex provide insights into how ELMO modulates DOCK activity and how Rac selectivity is achieved by ELMO.
Dimerization of DOCK2 Is Essential for DOCK2-Mediated Rac Activation and Lymphocyte Migration
TLDR
It is reported that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration, and fluorescence resonance energy transfer analyses revealedthat lobe A is required for Dock2 to activate Rac effectively during cell migration.
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