ArticleThe Journal of biological chemistry2012
R753Q polymorphism inhibits Toll-like receptor (TLR) 2 tyrosine phosphorylation, dimerization with TLR6, and recruitment of myeloid differentiation primary response protein 88.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 6 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 6 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Toll-like receptors polymorphisms and COVID-19: a systematic review.Molecular and cellular biochemistry · 2025Pooled it
- Association between TLR2 + 2477G/A polymorphism and bacterial meningitis: a meta-analysis.Epidemiology and infection · 2018Pooled it
- Genetic dissection of host immune response in pneumonia development and progression.Scientific reports · 2016Pooled it
- Identification of IDUA and WNT16 Phosphorylation-Related Non-Synonymous Polymorphisms for Bone Mineral Density in Meta-Analyses of Genome-Wide Association Studies.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Pooled it
- Association between the TLR2 Arg753Gln polymorphism and the risk of sepsis: a meta-analysis.Critical care (London, England) · 2015Pooled it
- Toll-like receptor -1, -2, and -6 polymorphisms and pulmonary tuberculosis susceptibility: a systematic review and meta-analysis.PloS one · 2013Pooled it
- Association between TLR2 polymorphisms (- 196-174 Ins/Del, R677W, R753Q, and P631H) and schizophrenia in a Tunisian population.Immunologic research · 2021Trial
- Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia.PloS one · 2016Trial
- Nanoadjuvant-integrated organic biomaterials for immune engineering: Mechanisms, design strategies, and translational applications.Materials today. Bio · 2026Review
- Bone and Infections: An Osteoimmunological Interplay.International journal of molecular sciences · 2026Review
- Exploratory Analysis of TLR2, TLR4, Interleukin 6 and Interleukin 10 Gene Polymorphisms in Relation to Clinical Early-Onset Sepsis in Preterm Neonates: A Single-Center Study.Life (Basel, Switzerland) · 2026Article
- Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026Review
- Review
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- Toll-like receptor 2-mediated downstream cytokine levels as determinant of malaria pathogenesis.The Indian journal of medical research · 2023Article
- Molecular characterization of four innate immune genes inFish and shellfish immunology reports · 2022Article
- Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches.International journal of molecular sciences · 2022Article
- The transmembrane adapter SCIMP recruits tyrosine kinase Syk to phosphorylate Toll-like receptors to mediate selective inflammatory outputs.The Journal of biological chemistry · 2022Article
- Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) Polymorphisms in Adult Patients with Acute B-cell Lymphoblastic Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE).Frontiers in allergy · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The R753Q polymorphism in the Toll-IL-1 receptor domain of Toll-like receptor 2 (TLR2) has been linked to increased incidence of tuberculosis and other infectious diseases, but the mechanisms by which it affects TLR2 functions are unclear. Here, we studied the impact of the R753Q polymorphism on TLR2 expression, hetero-dimerization with TLR6, tyrosine phosphorylation, and recruitment of myeloid differentiation primary response protein (MyD) 88 and MyD88 adapter-like (Mal). Complementation of HEK293 cells with transfected WT or R753Q TLR2 revealed their comparable total levels and only minimal changes in cell surface expression of the mutant species. Notably, even a 100-fold increase in amounts of transfected R753Q TLR2 versus WT variant did not overcome the compromised ability of the mutant TLR2 to activate nuclear factor κB (NF-κB), indicating that a minimal decrease in cell surface levels of the R753Q TLR2 cannot account for the signaling deficiency. Molecular modeling studies suggested that the R753Q mutation changes the electrostatic potential of the DD loop and results in a discrete movement of the residues critical for protein-protein interactions. Confirming these predictions, biochemical assays demonstrated that R753Q TLR2 exhibits deficient agonist-induced tyrosine phosphorylation, hetero-dimerization with TLR6, and recruitment of Mal and MyD88. These proximal signaling deficiencies correlated with impaired capacities of the R753Q TLR2 to mediate p38 phosphorylation, NF-κB activation, and induction of IL-8 mRNA in transfected HEK293 cells challenged with inactivated Mycobacterium tuberculosis or mycobacterial components. Thus, the R753Q polymorphism renders TLR2 signaling-incompetent by impairing its tyrosine phosphorylation, dimerization with TLR6, and recruitment of Mal and MyD88.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.