ArticleProceedings of the National Academy of Sciences of the United States of America2014
The GTPase-activating protein GIT2 protects against colitis by negatively regulating Toll-like receptor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- [Ubiquitination-mediated regulation of T cell homeostasis and autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Ubiquitin-Modifying Enzymes as Cell-Fate Regulators in Intestinal Inflammation.International journal of biological sciences · 2026Review
- TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways.Inflammation · 2025Article
- Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression.Animal models and experimental medicine · 2025Article
- Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow.Cancer cell · 2024Article
- Regulation of microtubule nucleation in mouse bone marrow-derived mast cells by ARF GTPase-activating protein GIT2.Frontiers in immunology · 2024Article
- Construction of a synthetic methodology-based library and its application in identifying a GIT/PIX protein-protein interaction inhibitor.Nature communications · 2022Article
- DSS-induced colitis activates the kynurenine pathway in serum and brain by affecting IDO-1 and gut microbiota.Frontiers in immunology · 2022Article
- Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.Frontiers in pharmacology · 2022Article
- HRD1-mediated METTL14 degradation regulates mMolecular cell · 2021Article
- Deubiquitylating enzymes: potential target in autoimmune diseases.Inflammopharmacology · 2021Review
- Energy supplementation rescues growth restriction and female infertility of mice with hepatic HRD1 ablation.American journal of translational research · 2020Article
- G Protein-Coupled Receptor Systems and Their Role in Cellular Senescence.Computational and structural biotechnology journal · 2019Review
- HRD1-ERAD controls production of the hepatokine FGF21 through CREBH polyubiquitination.The EMBO journal · 2018Article
- ER-associated ubiquitin ligase HRD1 programs liver metabolism by targeting multiple metabolic enzymes.Nature communications · 2018Article
- TRAF molecules in inflammation and inflammatory diseases.Current pharmacology reports · 2018Article
- Keratin 8 limits TLR-triggered inflammatory responses through inhibiting TRAF6 polyubiquitination.Scientific reports · 2016Article
- Expanding functions of GIT Arf GTPase-activating proteins, PIX Rho guanine nucleotide exchange factors and GIT-PIX complexes.Journal of cell science · 2016Review
- GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice.FEBS open bio · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptor kinase-interactor 2 (GIT2) regulates thymocyte positive selection, neutrophil-direction sensing, and cell motility during immune responses by regulating the activity of the small GTPases ADP ribosylation factors (Arfs) and Ras-related C3 botulinum toxin substrate 1 (Rac1). Here, we show that Git2-deficient mice were more susceptible to dextran sodium sulfate (DSS)-induced colitis, Escherichia coli, or endotoxin-shock challenge, and a dramatic increase in proinflammatory cytokines was observed in Git2 knockout mice and macrophages. GIT2 is a previously unidentified negative regulator of Toll-like receptor (TLR)-induced NF-κB signaling. The ubiquitination of TNF receptor associated factor 6 (TRAF6) is critical for the activation of NF-κB. GIT2 terminates TLR-induced NF-κB and MAPK signaling by recruiting the deubiquitinating enzyme Cylindromatosis to inhibit the ubiquitination of TRAF6. Finally, we show that the susceptibility of Git2-deficient mice to DSS-induced colitis depends on TLR signaling. Thus, we show that GIT2 is an essential terminator of TLR signaling and that loss of GIT2 leads to uncontrolled inflammation and severe organ damage.
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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.