Dock10, a novel CZH protein selectively induced by interleukin-4 in human B lymphocytes
Abstract
The Dock or CZH proteins are a family of activators for Rho GTPase proteins. The Zizimin subfamily is composed of three members: Dock9, Dock10, and Dock11. We have identified DOCK10 as an interleukin-4 (IL4)-inducible gene in chronic lymphocytic leukemias (CLLs). Subsequently, we have obtained the full-length cDNA sequence, which encodes a 2180 amino acid protein. Dock9 (2069 amino acids) and Dock11 (2073 amino acids) share more identity between them (58%) than with Dock10 (52% and 50%, respectively). Among normal human tissues, DOCK10 and DOCK11 mRNAs were mainly expressed in peripheral blood (PB) leukocytes. Dock10 protein was expressed at similar levels in normal PB-B and PB-T cells. Dock10 protein levels were heterogeneous in CLLs. IL4 consistently increased Dock10 mRNA and protein levels in CLL and normal PB-B cells. In contrast, IL4 did not affect the levels of Dock10 expression in normal PB-T cells. IL4 neither increased DOCK9 or DOCK11 mRNA levels in CLL cells. Dock10 protein distributed in the cytoplasm and nucleus of CLL cells, and IL4 increased its expression in both cellular compartments. The rapid and distinctive induction of Dock10 expression by IL4 in CLL and normal PB-B cells suggests a role for Dock10 in IL4-induced B-cell activation. Dock10 could represent a point of convergence for IL4 signalling and small Rho GTPase function in B cells.
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DOCK10 expression is induced by interleukin-4 (IL4).
“DOCK10 expression is reportedly induced by interleukin-4 (IL4), which activates signaling pathways involved in cell growth and differentiation (126).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [126]
In chronic lymphocytic leukemia (CLL), IL4 prolongs the survival of CLL cells.
“In chronic lymphocytic leukemia (CLL), IL4 prolongs the survival of CLL cells, which is linked to its known role in B-cell proliferation.”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [126]
Cites
The IL-4 receptor: signaling mechanisms and biologic functions
Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.701 · Cited by 1,545 · cited 1× · see citing works
“Interleukin-4 (IL4), upon binding to receptors (IL4R) expressed by a wide range of hematopoietic and non-hematopoietic cells, activates signalling cascades, including the IRS2, PI3K, and STAT6 pathways, which induce or modulate cell growth and differentiation processes (Nelms et al., 1999).”
BackgroundZizimin1, 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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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
“DOCK10 expression is reportedly induced by interleukin-4 (IL4), which activates signaling pathways involved in cell growth and differentiation (126).”
Background
- Authors
- Yelo, E., Bernardo, M. V., Gimeno, L., Alcaraz-García, M. J., Majado, M. J., & Parrado, A.
- Affiliations
- Hospital Universitario Virgen de la Arrixaca (ES)
- Corresponding author
- Parrado, Antonio
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 45
- Issue
- 12
- Pages
- 3411-3418
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W2040454232
- Cited by
- 46
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 1 · 2012: 4
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-4, chronic lymphocytic leukemia, B cells, B cell activation, gene induction, cDNA cloning, subcellular localization
- MeSH terms
- Amino Acid Sequence, B-Lymphocytes, Cloning, Molecular, Humans, Molecular Sequence Data, RNA, Messenger, Leukemia, Lymphocytic, Chronic, B-Cell, Interleukin-4, Gene Expression Regulation, Neoplastic, Lymphocyte Subsets, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Guanine Nucleotide Exchange Factors, Gene Expression Profiling, Protein Transport
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