Dock2 participates in bone marrow lympho-hematopoiesis
Open accessAbstract
Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although alpha4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.
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DOCK2 activates RAC GTPases and is predominantly expressed in hematopoietic cells.
“DOCK2, responsible for activating RAC GTPases, is predominantly expressed in hematopoietic cells (59, 60, 61, 62).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [62]
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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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- T. A. Springer, Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm, Cell 76 (1994) 301-314.
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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
- Authors
- Kikuchi, T., Kubonishi, S., Shibakura, M., Namba, N., Matsui, T., Fukui, Y., Tanimoto, M., & Katayama, Y.
- Affiliations
- Okayama University (JP)
- Kobe University (JP)
- Kyushu University (JP)
- Corresponding author
- Katayama, Yoshio
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 367
- Issue
- 1
- Pages
- 90-96
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2404560621
- Cited by
- 16
- References
- 1
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2016: 4 · 2014: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kobe University Repository Kernel (Kobe University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- DOCK2, bone marrow, hematopoietic stem cells, hematopoietic progenitor cells, CXCL12, chemotaxis, actin polymerization, Rac activation, CD49d, engraftment, 5-fluorouracil
- MeSH terms
- Actins, Animals, Bone Marrow, Chemotaxis, Fluorouracil, Hematopoiesis, Hematopoietic Stem Cells, Leukemia, Myeloid, Lymphocytes, Mice, Inbred C57BL, Stem Cells, Time Factors, Bone Marrow Transplantation, Receptors, CXCR4, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, Mice, Chemokine CXCL12
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