A Steric-Inhibition Model for Regulation of Nucleotide Exchange via the Dock180 Family of GEFs

@article{Lu2005ASM,
  title={A Steric-Inhibition Model for Regulation of Nucleotide Exchange via the Dock180 Family of GEFs},
  author={Mingjian Lu and Jason Michael Kinchen and Kent L. Rossman and Cynthia M. Grimsley and Matthew Hall and John Sondek and Michael O. Hengartner and Vijay Yajnik and Kodi S. Ravichandran},
  journal={Current Biology},
  year={2005},
  volume={15},
  pages={371-377}
}

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References

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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.
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
TLDR
A domain within Dock180 is identified that specifically recognizes nucleotide-free Rac and can mediate GTP loading of Rac in vitro and it is proposed that the Dock180–ELMO complex functions as an unconventional two-part exchange factor for Rac.
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.
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.
DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane.
TLDR
The results suggest that DOCK180 is a new effector molecule which transduces signals from tyrosine kinases through the CRK adaptor protein.
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DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1.
TLDR
It is found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain, and the association of Docks2 with ELMO1 is critical for Dock2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration.
Activation of Rac1 by a Crk SH3-binding protein, DOCK180.
TLDR
The results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling.
Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
TLDR
Sequence comparison combined with mutational analysis suggest that CZH2 is a new GEF domain for the Rho family of proteins, a new superfamily that includes the so-called 'CDM' proteins that bind to and activate Rac.
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