Evidence map›Paper›PMID 33684443›Full record

ReviewThe Journal of biological chemistry

RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors.

Andrew P Thompson, Christina Bitsina, Janine L Gray, Frank von Delft, Paul E Brennan

Open access · goldAbstract readReview
In one paragraph

Review in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Science advances · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Genes · 2023
    Review
  9. Article
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Andrew P ThompsonNuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Christina BitsinaNuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Janine L GrayNuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Frank von DelftNuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom; Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom; Department of Biochemistry, University of Johannesburg, Auckland Park, South Africa.
Paul E BrennanNuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, United Kingdom; Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom. Electronic address: paul.brennan@cmd.ox.ac.uk.
Nuffield Orthopaedic Centre · GBUniversity of Johannesburg · ZAUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human dedicator of cytokinesis (DOCK) family consists of 11 structurally conserved proteins that serve as atypical RHO guanine nucleotide exchange factors (RHO GEFs). These regulatory proteins act as mediators in numerous cellular cascades that promote cytoskeletal remodeling, playing roles in various crucial processes such as differentiation, migration, polarization, and axon growth in neurons. 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. Here, we provide an overview of the biological and structural characteristics for the various DOCK proteins and describe how they differ from other RHO GEFs and between DOCK subfamilies. The expression of the family varies depending on cell or tissue type, and they are consequently implicated in a broad range of disease phenotypes, particularly in the brain. A growing body of available structural information reveals the mechanism by which the catalytic DHR2 domain elicits nucleotide dissociation and also indicates strategies for the discovery and design of high-affinity small-molecule inhibitors. Such compounds could serve as chemical probes to interrogate the cellular function and provide starting points for drug discovery of this important class of enzymes.

Indexed as

Catalytic DomainGTP PhosphohydrolasesProtein ConformationRho Guanine Nucleotide Exchange FactorsGTP PhosphohydrolasesRho Guanine Nucleotide Exchange Factorscell signalingdedicator of cytokinesis (DOCK)drug discoveryguanine nucleotide exchange factorguanosine triphosphate (GTP)Ras homologous (RHO) small GTPasesstructural biology

Identifiers

PMID33684443
PMCPMC8063744
OpenAlexW3135782317

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.