ArticleBMC medicine2012
Germinal center kinase-like kinase (GLK/MAP4K3) expression is increased in adult-onset Still's disease and may act as an activity marker.
Article in BMC medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline.Zeitschrift fur Rheumatologie · 2023Review
- Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis.Frontiers in immunology · 2023Article
- SARS-CoV-2 spike protein enhances MAP4K3/GLK-induced ACE2 stability in COVID-19.EMBO molecular medicine · 2022Article
- Knockdown of circ-RAD23B inhibits non-small cell lung cancer progression via the miR-142-3p/MAP4K3 axis.Thoracic cancer · 2022Article
- Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus.Annals of the rheumatic diseases · 2022Article
- MAP4K3/GLK inhibits Treg differentiation by direct phosphorylating IKKβ and inducing IKKβ-mediated FoxO1 nuclear export and Foxp3 downregulation.Theranostics · 2022Article
- Comprehensive analysis of DNA methylation and gene expression profiles in gestational diabetes mellitus.Medicine · 2021Article
- Amino Acids in Autophagy: Regulation and Function.Advances in experimental medicine and biology · 2021Article
- Activation of c-Jun N-Terminal Kinase, a Potential Therapeutic Target in Autoimmune Arthritis.Cells · 2020Review
- Pathogenesis, disease course, and prognosis of adult-onset Still's disease: an update and review.Chinese medical journal · 2019Review
- MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus.Cells · 2019Review
- MAP4K3/GLK in autoimmune disease, cancer and aging.Journal of biomedical science · 2019Review
- AhR-ROR-γt complex is a therapeutic target for MAP4K3/GLKFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease.Science advances · 2018Article
- Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension.Protein science : a publication of the Protein Society · 2017Article
- Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase.Oncotarget · 2016Article
- GLK/MAP4K3 overexpression associates with recurrence risk for non-small cell lung cancer.Oncotarget · 2016Article
- Adult-onset Still's disease: current challenges and future prospects.Open access rheumatology : research and reviews · 2016Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGerminal center kinase-like kinase (GLK, also termed MAP4K3), a member of the MAP4K family, may regulate gene transcription, apoptosis and immune inflammation in response to extracellular signals. The enhanced expression of GLK has been shown to correspond with disease severity in patients with systemic lupus erythematosus. We investigated the role of GLK in the pathogenesis of adult-onset Still's disease, which shares some similar clinical characteristics with systemic lupus erythematosus.
methodsThe frequencies of circulating GLK-expressing T-cells in 24 patients with active adult-onset Still's disease and 12 healthy controls were determined by flow cytometry analysis. The expression levels of GLK proteins and transcripts were evaluated in peripheral blood mononuclear cells by immunoblotting and quantitative PCR. Serum levels of T helper (Th)17-related cytokines, including IL-1β, IL-6, IL-17 and TNF-α, were measured by ELISA.
resultsSignificantly higher median frequencies of circulating GLK-expressing T-cells were observed in patients with adult-onset Still's disease (31.85%) than in healthy volunteers (8.93%, P <0.001). The relative expression levels of GLK proteins and transcripts were also significantly higher in patients with adult-onset Still's disease (median, 1.74 and 2.35, respectively) compared with those in healthy controls (0.66 and 0.92, respectively, both P <0.001). The disease activity scores were positively correlated with the frequencies of circulating GLK-expressing T-cells (r = 0.599, P <0.005) and the levels of GLK proteins (r = 0.435, P <0.05) or GLK transcripts (r = 0.452, P <0.05) in patients with adult-onset Still's disease. Among the examined Th17-related cytokines, elevated levels of serum IL-6 and IL-17 were positively correlated with the frequencies of circulating GLK-expressing T-cells and the levels of GLK proteins as well as transcripts in patients with adult-onset Still's disease. GLK expression levels decreased significantly after effective therapy in these patients.
conclusionsElevated expression levels of GLK and their positive correlation with disease activity in patients with adult-onset Still's disease indicate that GLK may be involved in the pathogenesis and act as a novel activity biomarker of this disease.
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