ArticleThe EMBO journal2009
Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 116 citations in OpenAlex.
- Toll-like Receptor 8 (TLR8) Is Expressed in Mouse Hippocampal Neurons and Modulates Neuronal Excitability.International journal of molecular sciences · 2026Article
- Host-pathogen interactions during ESKAPE-mediated urinary tract infections and ventilator-associated pneumonia: a review.Folia microbiologica · 2026Review
- TLRs/PI3K/AKT1B Signaling Pathway Is Involved in Modulation of Neuroinflammation in the Rat Hippocampus by Alpha-pinene in Morphine-dependent and Withdrawing Rats.Neurochemical research · 2025Article
- Myeloid Differentiation Primary Response Protein 88: An Important Therapeutic Target for Chronic Pain.Journal of pain research · 2025Review
- Toll-like receptor adaptor protein TIRAP has specialized roles in signaling, metabolic control and leukocyte migration upon wounding in zebrafish larvae.International journal of biological sciences · 2025Article
- Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer.Chembiochem : a European journal of chemical biology · 2024Article
- Interactions Between Bovine Respiratory Syncytial Virus and Cattle: Aspects of Pathogenesis and Immunity.Viruses · 2024Review
- Sulfate-Reducing Bacteria Induce Pro-Inflammatory TNF-α and iNOS via PI3K/Akt Pathway in a TLR 2-Dependent Manner.Microorganisms · 2024Article
- Characterization of extracellular vesicles from Lactiplantibacillus plantarum.Scientific reports · 2022Article
- Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases.Journal of clinical medicine · 2022Review
- AKT Isoforms in Macrophage Activation, Polarization, and Survival.Current topics in microbiology and immunology · 2022Article
- Sterile alpha and TIR motif-containing protein 1 is a negative regulator in the anti-bacterial immune responses in nile tilapia (Frontiers in immunology · 2022Article
- Toll receptors remodel epithelia by directing planar-polarized Src and PI3K activity.Developmental cell · 2021Article
- Strategies for Biomaterial-Based Spinal Cord Injury RepairFrontiers in bioengineering and biotechnology · 2021Review
- TIRAP in the Mechanism of Inflammation.Frontiers in immunology · 2021Review
- Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer.Cancer science · 2020Article
- Article
- INH14, a Small-Molecule Urea Derivative, Inhibits the IKKα/β-Dependent TLR Inflammatory Response.Chembiochem : a European journal of chemical biology · 2019Article
- Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Insight into Phosphatidylinositol-Dependent Membrane Localization of the Innate Immune Adaptor Protein Toll/Interleukin 1 Receptor Domain-Containing Adaptor Protein.Frontiers in immunology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The recognition of bacterial lipoproteins by toll-like receptor (TLR) 2 is pivotal for inflammation initiation and control in many bacterial infections. TLR2-dependent signalling is currently believed to essentially require both adaptor proteins MyD88 (myeloid differentiation primary response gene 88) and Mal/TIRAP (MyD88-adapter-like/TIR-domain-containing adaptor protein). TLR2-dependent, but MyD88-independent responses have not been described yet. We report here on a novel-signalling pathway downstream of TLR2, which does not adhere to the established model. On stimulation of the TLR2/6 heterodimer with diacylated bacterial lipoproteins, Mal directly interacts with the regulatory subunit of phosphoinositide 3-kinase (PI3K), p85alpha, in an inducible fashion. The Mal-p85alpha interaction drives PI3K-dependent phosphorylation of Akt, phosphatidylinositol(3,4,5)P3 (PIP(3)) generation and macrophage polarization. MyD88 is not essential for PI3K activation and Akt phosphorylation; however, cooperates with Mal for PIP(3) formation and accumulation at the leading edge. In contrast to TLR2/6, TLR2/1 does not require Mal or MyD88 for Akt phosphorylation. Hence, Mal specifically connects TLR2/6 to PI3K activation, PIP(3) generation and macrophage polarization.
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.