ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Dok-4 is a novel negative regulator of T cell activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- PRECOG update: an augmented resource of clinical outcome associations with gene expression for adult, pediatric, and immunotherapy cohorts.Nucleic acids research · 2026Article
- Pan-cancer analysis reveals age-associated genetic alterations in protein domains.American journal of human genetics · 2025Article
- New insights into the genetic predisposition of brucellosis and its effect on the gut and vaginal microbiota in goats.Scientific reports · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.Respiratory research · 2022Article
- Comprehensive analysis of DOK family genes expression, immune characteristics, and drug sensitivity in human tumors.Journal of advanced research · 2022Article
- Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis.Clinics (Sao Paulo, Brazil) · 2018Review
- Adipocyte morphology and implications for metabolic derangements in acquired obesity.International journal of obesity (2005) · 2014Article
- Dok1 and Dok2 proteins regulate natural killer cell development and function.The EMBO journal · 2014Article
- Constitutive AKT activation in follicular lymphoma.BMC cancer · 2014Article
- An Emerging Role for PI5P in T Cell Biology.Frontiers in immunology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dok-4 (downstream of tyrosine kinase-4) is a recently identified member of the Dok family of adaptor proteins, which are characterized by an amino-terminal pleckstrin homology domain, a phosphotyrosine-binding domain, and a carboxyl-terminal region containing several tyrosines and poly-proline-rich motifs. Two members of the Dok family, Dok-1 and Dok-2, have already been described as negative regulators in T cells. However, the function of Dok-4, which is also expressed in T cells, remains unknown. In this study, we report that Dok-4 is phosphorylated after TCR engagement and shuttled within the cytoplasm of T cells before being recruited to the polarized microtubule organizing center after the formation of the immunological synapse. Loss-of-function experiments using RNA interference constructs show that Dok-4 is a negative regulator of ERK phosphorylation, IL-2 promoter activity, and T cell proliferation. Exogenous expression of wild-type Dok-4 induces a significant activation of Rap1, which is involved in the regulation of ERK. The pleckstrin homology domain of Dok-4 is required both for its cytoplasmic shuttling and relocalization as well as for its inhibitory properties on T cell activation. Thus, Dok-4 represents a novel negative regulator of T cells.
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Registered trials
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