ArticleThe Journal of biological chemistry2014
A coding IRAK2 protein variant compromises Toll-like receptor (TLR) signaling and is associated with colorectal cancer survival.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression.Journal of innate immunity · 2024Article
- Tumor Necrosis Factor Receptor-Associated Factor 6 and Human Cancer: A Systematic Review of Mechanistic Insights, Functional Roles, and Therapeutic Potential.Journal of Cancer · 2024Review
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- Interleukin-17-A multifaceted cytokine in viral infections.Journal of cellular physiology · 2021Review
- IRAK2, an IL1R/TLR Immune Mediator, Enhances RadiosensitivityFrontiers in oncology · 2021Article
- A Random Walk-Based Method to Identify Candidate Genes Associated With Lymphoma.Frontiers in genetics · 2021Article
- Putative link between Polo-like kinases (PLKs) and Toll-like receptor (TLR) signaling in transformed and primary human immune cells.Scientific reports · 2019Article
- Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.PloS one · 2018Article
- Nucleotide-binding mechanisms in pseudokinases.Bioscience reports · 2015Review
- CHOP links endoplasmic reticulum stress to NF-κB activation in the pathogenesis of nonalcoholic steatohepatitis.Molecular biology of the cell · 2015Article
- The structural basis for cancer treatment decisions.Oncotarget · 2014Review
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Within innate immune signaling pathways, interleukin-1 receptor-associated kinases (IRAKs) fulfill key roles downstream of multiple Toll-like receptors and the interleukin-1 receptor. Although human IRAK4 deficiency was shown to lead to severe immunodeficiency in response to pyogenic bacterial infection during childhood, little is known about the role of human IRAK2. We here identified a non-synonymous IRAK2 variant, rs35060588 (coding R214G), as hypofunctional in terms of NF-κB signaling and Toll-like receptor-mediated cytokine induction. This was due to reduced ubiquitination of TRAF6, a key step in signal transduction. IRAK2 rs35060588 occurs in 3-9% of individuals in different ethnic groups, and our studies suggested a genetic association of rs35060588 with colorectal cancer survival. This for the first time implicates human IRAK2 in a human disease and highlights the R214G IRAK2 variant as a potential novel and broadly applicable biomarker for disease or as a therapeutic intervention point.
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