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Cited by 17Protein Kinase Regulation and GTPase SignalingCellular transport and secretionCellular Mechanics and Interactions

Zizimin and Dock guanine nucleotide exchange factors in cell function and disease

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Pakes, Nicholl K., Veltman, Douwe M., Williams, Robin S.B.·2013·Small GTPases
DOI 10.4161/sgtp.22087PMC PMC3620097
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Abstract

Zizimin proteins belong to the Dock (Dedicator of Cytokinesis) superfamily of Guanine nucleotide Exchange Factor (GEF) proteins. This family of proteins plays a role in the regulation of Rho family small GTPases. Together the Rho family of small GTPases and the Dock/Zizimin proteins play a vital role in a number of cell processes including cell migration, apoptosis, cell division and cell adhesion. Our recent studies of Zizimin proteins, using a simple biomedical model, the eukaryotic social amoeba Dictyostelium discoideum, have helped to elucidate the cellular role of these proteins. In this article, we discuss the domain structure of Zizimin proteins from an evolutionary viewpoint. We also compare what is currently known about the mammalian Zizimin proteins to that of related Dock proteins. Understanding the cellular functions of these proteins will provide a better insight into their role in cell signaling, and may help in treating disease pathology associated with mutations in Dock/Zizimin proteins.

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  • DOCK DHR2 domains facilitate nucleotide dissociation from small GTPases, a process otherwise too slow for rapid spatiotemporal control of cellular signaling.

    “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 [33]

    The Introduction (page not available in our copy) says the DHR2 domain is responsible for guanine nucleotide exchange factor activity, supporting the claim that it facilitates nucleotide exchange in small GTPases. It does not address the rate of nucleotide dissociation without a GEF or say that it is too slow for rapid spatiotemporal control of signaling. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The DHR2 domain is responsible for GEF activity in a mechanism distinct from that of DH-containing GEFs.

    “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 [33]

    The Introduction states that the DHR2 domain is responsible for GEF activity. It does not describe the mechanism or compare it with that of DH-containing GEFs, so the claimed mechanistic distinction is not supported by this paper's text. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Pakes, N. K., Veltman, D. M., & Williams, R. S. B.
Affiliations
  • Royal Holloway University of London (GB)
  • Cancer Research UK Scotland Institute (GB)
Corresponding author
  • Veltman, Douwe M.
  • Williams, Robin S.B.
ORCID
Venue
Small GTPases
Publisher
Informa UK Limited
Published
2013-01
Volume
4
Issue
1
Pages
22-27
ISSN
  • 2154-1248 (ISSN-L)
  • 2154-1256
DOI
10.4161/sgtp.22087
PMC
PMC3620097
OpenAlex
W2067374493
Cited by
17
References
2
Citations by year
2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2018: 1 · 2017: 2 · 2015: 2 · 2014: 2 · 2013: 2
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Small GTPases (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Centre for the Replacement, Refinement and Reduction of Animals in Research (G0900775/1)
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
guanine nucleotide exchange factor, Rho GTPases, Dictyostelium discoideum, cell migration, apoptosis, cell division, cell adhesion, protein domain structure, evolution, signal transduction, pathogenic variants
MeSH terms
Animals, Dictyostelium, Biological Evolution, Humans, Mutation, Phylogeny, Protozoan Proteins, Protein Structure, Tertiary, Guanine Nucleotide Exchange Factors

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