ArticleJournal of leukocyte biology2014
The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4.
Article in Journal of leukocyte biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Review
- RANKL inhibits macrophage proinflammatory Toll-like receptor 2 and 4 signaling and impairs killing of intracellular bacteria.ImmunoHorizons · 2026Article
- The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Ticam2 ablation facilitates monocyte exhaustion recovery after sepsis.Scientific reports · 2025Article
- Structural and immunological impacts of TOLLIP nsSNPs: A computational biology approach to drug discovery and immune system modulation.PloS one · 2025Article
- Dose-Dependent Effects of Lipopolysaccharide on the Endothelium-Sepsis versus Metabolic Endotoxemia-Induced Cellular Senescence.Antioxidants (Basel, Switzerland) · 2024Review
- Crosstalk Between Autophagy and Inflammation in Chronic Cerebral Ischaemia.Cellular and molecular neurobiology · 2023Review
- Regulation of innate immune signaling by IRAK proteins.Frontiers in immunology · 2023Review
- A genome-wide search of Toll/Interleukin-1 receptor (TIR) domain-containing adapter molecule (TICAM) and their evolutionary divergence from other TIR domain containing proteins.Biology direct · 2022Article
- The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.Cell reports · 2022Article
- Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling.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
- Review
- Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway.Biomedicines · 2020Article
- Toll-Like Receptor as a Potential Biomarker in Renal Diseases.International journal of molecular sciences · 2020Review
- Progressive Skeletal Muscle Atrophy in Muscular Dystrophies: A Role for Toll-like Receptor-Signaling in Disease Pathogenesis.International journal of molecular sciences · 2020Review
- Review
- Polarization of Low-Grade Inflammatory Monocytes Through TRAM-Mediated Up-Regulation of Keap1 by Super-Low Dose Endotoxin.Frontiers in immunology · 2020Article
- Two-layer regulation ofAmerican journal of translational research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 5 countries.
Funding
Abstract
TLRs act as sentinels in professional immune cells to detect and initiate the innate immune response to pathogen challenge. TLR4 is a widely expressed TLR, responsible for initiating potent immune responses to LPS. TRAM acts to bridge TLR4 with TRIF, orchestrating the inflammatory response to pathogen challenge. We have identified a putative TRAF6-binding motif in TRAM that could mediate a novel signaling function for TRAM in TLR4 signaling. TRAM and TRAF6 association was confirmed by immunoprecipitation of endogenous, ectopically expressed and recombinant proteins, which was ablated upon mutation of a key Glu residue in TRAM (TRAM E183A). TRAF6 and TRAM were observed colocalizing using confocal microscopy following ectopic expression in cells and the ability of TRAM and TRAM E183A to activate luciferase-linked reporter assays was determined in HEK293 and TRAF6-deficient cells. Importantly, TRAM-deficient macrophages reconstituted with TRAM E183A display significantly reduced inflammatory TNF-α, IL-6, and RANTES protein production compared with WT TRAM. These results demonstrate a novel role for TRAM in TLR4-mediated signaling in regulating inflammatory responses via its interaction with TRAF6, distinct from its role as a bridging adaptor between TLR4 and TRIF.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.