DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1
Open accessAbstract
Although the migratory property of lymphocytes is critical for protective immunity, tissue infiltration of lymphocytes sometimes causes harmful immune responses. DOCK2 plays a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation, yet the mechanism by which DOCK2 activates Rac remains unknown. We found that DOCK2 associates with engulfment and cell motility (ELMO1) through its Srchomology 3 (SH3) domain. When DOCK2 was expressed in T-hybridoma cells lacking endogenous expression of DOCK2, Rac activation and actin polymerization were induced. However, such responses were not elicited by the DOCK2 mutant lacking the region required for ELMO1 binding. On the other hand, we found that the expression of ELMO1 induces Rac activation in the plasmacytoma cells expressing DOCK2 but not ELMO1. These results indicate that the association of DOCK2 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.
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The physiological activation of Rac by DOCK2 and DOCK180 requires their association with a regulatory protein ELMO1.
“Interestingly, the physiological activation of Rac by these GEFs requires their association with a regulatory protein ELMO1 (Engulfment and Motility) (6,33,34).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [34]
The Results and discussion section says DOCK2’s interaction with ELMO1 is required for Rac activation in the tested cells. The Introduction says ELMO1 associates with DOCK180 and cooperatively regulates Rac activation, but does not establish that the association is required for DOCK180. No page numbers are provided in our copy. (LLM, conf=0.85)
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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
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Insights into TREM2 biology by network analysis of human brain gene expression data
Forabosco, P., Ramasamy, A., Trabzuni, D., Walker, R., Smith, C., Bras, J., Levine, A. P., Hardy, J., Pocock, J. M., Guerreiro, R., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.001 · Cited by 180 · see citing works
Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors
Kwofie, M. A., & Skowronski, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705170200 · Cited by 36 · see citing works
- Authors
- Sanui, T., Inayoshi, A., Noda, M., Iwata, E., Stein, J. V., Sasazuki, T., & Fukui, Y.
- Affiliations
- Kyushu University (JP)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-10-15
- Volume
- 102
- Issue
- 8
- Pages
- 2948-2950
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1976233823
- Cited by
- 120
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 9
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- DOCK2, ELMO1, Rac activation, actin cytoskeleton remodeling, lymphocyte migration, SH3 domain, actin polymerization, plasmacytoma cells, lymphocyte infiltration, immune disorders
- MeSH terms
- Actins, Carrier Proteins, Cell Line, Cell Movement, Cytoskeleton, Genetic Vectors, Humans, Lymphocytes, Microscopy, Fluorescence, Plasmids, Precipitin Tests, Protein Binding, Transfection, Immunoblotting, Protein Structure, Tertiary, src Homology Domains, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Adaptor Proteins, Signal Transducing
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