The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
Abstract
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.
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“At the molecular level, DOCK DHR2 domains facilitate nucleotide dissociation from small GTPases, a process that is otherwise too slow for rapid spatiotemporal control of cellular signaling.”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [34]
In the citing paper
“Uniquely, the DOCK-D proteins contain a PH domain, which, similarly to the DHR1 domain, is involved in membrane localization through phospholipid binding (34).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [34]
In the citing paper
“The DHR2 domain is responsible for GEF activity in a mechanism that is distinct from that of DH-containing GEFs (33, 34, 35).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [34]
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Metadata
- Authors
- Brugnera, E., Haney, L., Grimsley, C., Lu, M., Walk, S. F., Tosello-Trampont, A.-C., Macara, I. G., Madhani, H., Fink, G. R., & Ravichandran, K. S.
- Affiliations
- University of Virginia (US)
- University of California, San Francisco (US)
- Whitehead Institute for Biomedical Research (US)
- Venue
- Nature Cell Biology
- Published
- 2002-07-15
- Volume
- 4
- Issue
- 8
- Pages
- 574-582
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2069986934
- Cited by
- 576
- References
- 33
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 16 · 2023: 16 · 2022: 21 · 2021: 19 · 2020: 9 · 2019: 21 · 2018: 17 · 2017: 18 · 2016: 24 · 2015: 16 · 2014: 25 · 2013: 32 · 2012: 33
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- DOCK180, ELMo, Rac GTPase, GTP loading, Rac1, cell migration, Rho GTPase signaling
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Cell Line, Cytoskeletal Proteins, Guanosine Triphosphate, Humans, Molecular Sequence Data, Phagocytosis, Proteins, Recombinant Proteins, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Guanine Nucleotide Exchange Factors, rac GTP-Binding Proteins, Caenorhabditis elegans Proteins, Macromolecular Substances, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins
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