The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration
Abstract
Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics, both of which are regulated by Rho family GTPases. Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement. The CDM family proteins, Caenorhabditis elegans CED-5, human DOCK180 and Drosophila melanogaster Myoblast City (MBC), are implicated to mediate membrane extension by functioning upstream of Rac. Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells, physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is indispensable for lymphocyte chemotaxis. DOCK2-deficient mice (DOCK2-/-) exhibited migration defects of T and B lymphocytes, but not of monocytes, in response to chemokines, resulting in several abnormalities including T lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. In DOCK2-/- lymphocytes, chemokine-induced Rac activation and actin polymerization were almost totally abolished. Thus, in lymphocyte migration DOCK2 functions as a central regulator that mediates cytoskeletal reorganization through Rac activation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“DOCK2 activates Rac but not Cdc42, whereas DOCK9 activates Cdc42 but not Rac (6,35,38).”
From Specific Recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 Guanine Nucleotide Exchange Factors (2008) · cites this paper as [6]
In the citing paper
“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 [6]
Citations
Cites
Rho GTPases and the Actin Cytoskeleton
Hall, A. (1998) · Science · doi:10.1126/science.279.5350.509 · Cited by 6,138
Cell Migration: A Physically Integrated Molecular Process
Lauffenburger, D. A., & Horwitz, A. F. (1996) · Cell · doi:10.1016/s0092-8674(00)81280-5 · Cited by 3,915
Förster, R., Schubel, A., Breitfeld, D., Kremmer, E., Renner‐Müller, I., Wolf, E., & Lipp, M. (1999) · Cell · doi:10.1016/s0092-8674(00)80059-8 · Cited by 2,348
The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry
Bleul, C. C., Farzan, M., Choe, H., Parolin, C., Clark‐Lewis, I., Sodroski, J., & Springer, T. A. (1996) · Nature · doi:10.1038/382829a0 · Cited by 1,953
Oberlin, E., Amara, A., Bachelerie, F., Chable-Bessia, C., Virelizier, J., Arenzana‐Seisdedos, F., Schwartz, O., Heard, J., Clark‐Lewis, I., Legler, D. F., et al. (1996) · Nature · doi:10.1038/382833a0 · Cited by 1,652
A brain serine/threonine protein kinase activated by Cdc42 and Rac1
Manser, E. J., Leung, T., Salihuddin, H., Zhao, Z.-S., & Lim, L. (1994) · Nature · doi:10.1038/367040a0 · Cited by 1,541
Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
Hirsch, E., Katanaev, V. L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F., & Wymann, M. P. (2000) · Science · doi:10.1126/science.287.5455.1049 · Cited by 1,209
Förster, R., Mattis, A. E., Kremmer, E., Wolf, E., Brem, G., & Lipp, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81798-5 · Cited by 1,129
Function of PI3Kγ in Thymocyte Development, T Cell Activation, and Neutrophil Migration
Sasaki, T., Irie-Sasaki, J., Jones, R. G., Oliveira-dos-Santos, A., Stanford, W. L., Bolon, B. N., Wakeham, A. C., Itié, A., Bouchard, D., Kozieradzki, I., et al. (2000) · Science · doi:10.1126/science.287.5455.1040 · Cited by 1,027
Gunn, M. D., Kyuwa, S., Tam‐Amersdorfer, C., Kakiuchi, T., Matsuzawa, A., Williams, L. T., & Nakano, H. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.3.451 · Cited by 1,019
Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis
Servant, G., Weiner, O. D., Herzmark, P., Balla, T., Sedat, J. W., & Bourne, H. R. (2000) · Science · doi:10.1126/science.287.5455.1037 · Cited by 878
Roles of PLC-β2 and -β3 and PI3Kγ in Chemoattractant-Mediated Signal Transduction
Li, Z., Jiang, H., Xie, W., Zhang, Z., Smrcka, A. V., & Wu, D. (2000) · Science · doi:10.1126/science.287.5455.1046 · Cited by 807
Bar‐Sagi, D., & Hall, A. (2000) · Cell · doi:10.1016/s0092-8674(00)00115-x · Cited by 800
Dancing to the tune of chemokines
Thelen, M. (2001) · Nature Immunology · doi:10.1038/84224 · Cited by 620
A Role for Cdc42 in Macrophage Chemotaxis
Allen, W. E., Zicha, D., Ridley, A. J., & Jones, G. E. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.5.1147 · Cited by 528
Activation of Rac1 by a Crk SH3-binding protein, DOCK180Preprint
Kiyokawa, E., Hashimoto, Y., Kobayashi, S., Sugimura, H., Kurata, T., & Matsuda, M. (1998) · Genes & Development · doi:10.1101/gad.12.21.3331 · Cited by 431
Oliver, A. M., Martin, F., Gartland, G. L., Carter, R. H., & Kearney, J. F. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270935 · Cited by 427
CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans
Reddien, P. W., & Horvitz, H. R. (2000) · Nature Cell Biology · doi:10.1038/35004000 · Cited by 414
Stowers, L., Yelon, D. L., Berg, L. J., & Chant, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.5027 · Cited by 381
C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180
Wu, Y., & Horvitz, H. R. (1998) · Nature · doi:10.1038/33163 · Cited by 365
DOCK180, a Major CRK-Binding Protein, Alters Cell Morphology upon Translocation to the Cell Membrane
Hasegawa, H., Kiyokawa, E., Tanaka, S., Nagashima, K., Gotoh, N., Shibuya, M., Kurata, T., & Matsuda, M. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1770 · Cited by 335
Secondary Lymphoid-tissue Chemokine Is a Functional Ligand for the CC Chemokine Receptor CCR7
Yoshida, R., Nagira, M., Kitaura, M., Imagawa, N., Imai, T., & Yoshie, O. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.12.7118 · Cited by 320
Erickson, M. R. S., Galletta, B. J., & Abmayr, S. M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.3.589 · Cited by 255
Nolan, K. M., Barrett, K., Lu, Y., Hu, K.-Q., Vincent, S., & Settleman, J. E. (1998) · Genes & Development · doi:10.1101/gad.12.21.3337 · Cited by 201
Nakano, H., Mori, S., Yonekawa, H., Nariuchi, H., Matsuzawa, A., & Kakiuchi, T. (1998) · Blood · doi:10.1182/blood.v91.8.2886.2886_2886_2895 · Cited by 186
Differential Chemotactic Behavior of Developing T Cells in Response to Thymic Chemokines
Kim, C. H., Pelus, L. M., White, J. R., & Broxmeyer, H. E. (1998) · Blood · doi:10.1182/blood.v91.12.4434 · Cited by 172
Phosphoinositide 3‐kinase: a key biochemical signal for cell migration in response to chemokines
Sotsios, Y., & Ward, S. G. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.17712.x · Cited by 145
Onai, N., Zhang, Y., Yoneyama, H., Kitamura, T., Ishikawa, S., & Matsushima, K. (2000) · Blood · doi:10.1182/blood.v96.6.2074 · Cited by 104
Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins
Nishihara, H., Kobayashi, S., Hashimoto, Y., Ohba, F., Mochizuki, N., Kurata, T., Nagashima, K., & Matsuda, M. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(99)00133-0 · Cited by 100
Flagged first, then by citations
Cited by
Sorted by citations
Cell migration: Rho GTPases lead the way
Raftopoulou, M., & Hall, A. (2003) · Developmental Biology · doi:10.1016/j.ydbio.2003.06.003 · Cited by 1,494
Martin, F., & Kearney, J. F. (2002) · Nature reviews. Immunology · doi:10.1038/nri799 · Cited by 867
Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes
Cerutti, A., Cols, M., & Puga, I. (2013) · Nature reviews. Immunology · doi:10.1038/nri3383 · Cited by 837
Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis
Funamoto, S., Meili, R., Lee, S. D., Parry, L. A., & Firtel, R. (2002) · Cell · doi:10.1016/s0092-8674(02)00755-9 · Cited by 746
Combined Immunodeficiency Associated with DOCK8 Mutations
Zhang, Q., Davis, J. C., Lamborn, I. T., Freeman, A. F., Jing, H., Favreau, A. J., Matthews, H. F., Davis, J., Turner, M. L. C., Uzel, G., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0905506 · Cited by 741
Metadata
- Authors
- Fukui, Y., Hashimoto, O., Sanui, T., Oono, T., Koga, H., Abe, M., Inayoshi, A., Noda, M., Oike, M., Shirai, T., & Sasazuki, T.
- Affiliations
- Kyushu University (JP)
- Kurume University (JP)
- Juntendo University (JP)
- Corresponding author
- Shirai, Toshikazu
- ORCID
- Venue
- Nature
- Published
- 2001-08
- Volume
- 412
- Issue
- 6849
- Pages
- 826-831
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2022157262
- Cited by
- 449
- References
- 30
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 14 · 2018: 15 · 2017: 18 · 2016: 10 · 2015: 12 · 2014: 23 · 2013: 21 · 2012: 22
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Michigan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- DOCK2, lymphocyte chemotaxis, lymphocyte migration, Rac activation, Rho GTPases, actin polymerization, cytoskeletal remodeling, T cells, B cells, marginal zone B cells, lymphopenia, chemokines
- MeSH terms
- Animals, B-Lymphocytes, Carrier Proteins, Cell Line, Chemotaxis, Leukocyte, Cytoskeleton, Female, Hematopoietic Stem Cells, Immunologic Memory, Male, Mice, Inbred C57BL, Spleen, Stem Cells, T-Lymphocytes, Cytokines, Chemokines, CXC, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, Mice, Chemokine CXCL12
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
