Immune regulatory functions of DOCK family proteins in health and disease
Abstract
DOCK proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in GEFs, they mediate the GTP-GDP exchange reaction through DHR-2 domain. Accumulating evidence indicates that the DOCK proteins act as major GEFs in varied biological settings. For example, DOCK2, which is predominantly expressed in hematopoietic cells, regulates migration and activation of leukocytes through Rac activation. On the other hand, it was recently reported that mutations of DOCK8, another member of the DOCK family proteins, cause a combined immunodeficiency syndrome in humans. This article reviews the structure, functions and signaling of DOCK2 and DOCK8, especially focusing on their roles in immune responses.
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DOCK11 is highly expressed in B and T lymphocytes.
“DOCK11 is a CDC42-specific GEF that is highly expressed in B and T lymphocytes and has been shown to participate in B-cell homeostasis and differentiation mechanisms (94, 97, 128).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [97]
DOCK11 is a CDC42-specific GEF.
“DOCK11 is a CDC42-specific GEF that is highly expressed in B and T lymphocytes and has been shown to participate in B-cell homeostasis and differentiation mechanisms (94, 97, 128).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [97]
DOCK11 participates in B-cell homeostasis and differentiation mechanisms.
“DOCK11 is a CDC42-specific GEF that is highly expressed in B and T lymphocytes and has been shown to participate in B-cell homeostasis and differentiation mechanisms (94, 97, 128).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [97]
Cites
Unconventional Rac-GEF activity is mediated through the Dock180–ELMO complex
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. (2002) · Nature Cell Biology · doi:10.1038/ncb824 · Cited by 576 · see citing works
Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration
Fukui, Y., Hashimoto, O., Sanui, T., Oono, T., Koga, H., Abe, M., Inayoshi, A., Noda, M., Oike, M., Shirai, T., et al. (2001) · Nature · doi:10.1038/35090591 · Cited by 449 · see citing works
Self-citationZizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller, N., Irani-Tehrani, M., Kiosses, W. B., Del Pozo, M. A., & Schwartz, M. A. (2002) · Nature Cell Biology · doi:10.1038/ncb835 · Cited by 171 · see citing works
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Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions
Martins, R., Maier, J., Gorki, A.-D., Huber, K. V. M., Sharif, O., Starkl, P., Saluzzo, S., Quattrone, F., Gawish, R., Lakovits, K., et al. (2016) · Nature Immunology · doi:10.1038/ni.3590 · Cited by 142 · see citing works
Mehta, D., Bruenig, D., Carrillo‐Roa, T., Lawford, B., Harvey, W., Morris, C. P., Smith, A. K., Binder, E. B., Young, R. M., & Voisey, J. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12778 · Cited by 78 · see citing works
Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
“DOCK11 is a CDC42-specific GEF that is highly expressed in B and T lymphocytes and has been shown to participate in B-cell homeostasis and differentiation mechanisms (94, 97, 128).”
Background
- Authors
- Nishikimi, A., Kukimoto-Niino, M., Yokoyama, S., & Fukui, Y.
- Affiliations
- Kyushu University (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Fukui, Yoshinori
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 319
- Issue
- 15
- Pages
- 2343-2349
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W1981478417
- Cited by
- 80
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 9 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 4 · 2014: 8 · 2013: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- DOCK2, DOCK8, guanine nucleotide exchange factor, Rho GTPases, Rac activation, leukocyte migration, leukocyte activation, combined immunodeficiency, immune regulation, hematopoietic cells
- MeSH terms
- Cell Differentiation, Cell Movement, Dendritic Cells, Gene Expression Regulation, Humans, Interferon Type I, Models, Molecular, Mutation, T-Lymphocytes, Signal Transduction, Severe Combined Immunodeficiency, Protein Structure, Tertiary, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins
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