ArticleScientific reports2017
Reciprocal regulation of TLR2-mediated IFN-β production by SHP2 and Gsk3β.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Lactococcus lactis-HSP65 requires TLR2 to induce tolerogenic dendritic cells and confer protection against type 1 diabetes in a murine model.Cellular and molecular life sciences : CMLS · 2025Article
- TLR2 agonism suppresses myeloid leukemogenesis by reprogramming leukemia stem cells.Blood advances · 2025Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- (+)-Naloxone blocks Toll-like receptor 4 to ameliorate deleterious effects of stress on male mouse behaviors.Brain, behavior, and immunity · 2020Article
- An alternative model for type I interferon induction downstream of human TLR2.The Journal of biological chemistry · 2020Article
- SHP2 deficiency promotes Staphylococcus aureus pneumonia following influenza infection.Cell proliferation · 2020Article
- Innate Immune Recognition: An Issue More Complex Than Expected.Frontiers in cellular and infection microbiology · 2019Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 2 (TLR2) mediates the innate immune response to bacterial lipopeptides and peptidoglycans by stimulating the production of inflammatory cytokines. However, the mechanisms by which TLR2 signaling regulates type I interferon (IFN)-β production are poorly understood. Here, we identified Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) as a negative regulator of TLR2-induced IFN-β production. Pharmacological inhibition or reduced expression of SHP2 potentiated TLR2 agonist-mediated IFN-β transcription and STAT1 activation, whereas overexpression of SHP2 impaired IFN-β transcription and STAT1 activation. SHP2 physically associated with the glycogen synthase kinase 3β (Gsk3β) in an agonist-dependent manner. Gsk3β positively regulates transcription of IFN-β following TLR2 stimulation by inhibiting the phosphorylation of SHP2. SHP2 inhibited the transcriptional activity of IRF-1 and IRF-8 at the IFN-β promoter. Remarkably, IRF-1 and IRF-8 are recruited to the IFN-β promoter in a SHP2 phosphatase activity-dependent manner. These findings provide insight into the mechanisms by which SHP2 and Gsk3β work together to modulate TLR2-mediated IFN-β production in macrophages.
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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.