ArticleJournal of immunology (Baltimore, Md. : 1950)2006
Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins.
Article in Journal of immunology (Baltimore, Md. : 1950), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 199 citations in OpenAlex.
- Trial
- Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003.British journal of haematology · 2015Trial
- Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia.British journal of clinical pharmacology · 2013Trial
- Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy.British journal of pharmacology · 2010Trial
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genesFrontiers in immunology · 2026Article
- PACSIN2 regulates mercaptopurine cytotoxicity and cellular biomechanics through Rac1 modulation in intestinal epithelial cells.Frontiers in pharmacology · 2026Article
- Characterisation of autophagy induction by the thiopurine drugs azathioprine, mercaptopurine and thioguanine in THP-1 macrophages.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Post-translational modification in the pathogenesis of vitiligo.Immunologic research · 2024Review
- Thrombospondin 1 and Reelin act through Vldlr to regulate cardiac growth and repair.Basic research in cardiology · 2024Article
- Article
- Role of Rho GTPases in inflammatory bowel disease.Cell death discovery · 2023Review
- Thiopurines inhibit coronavirus Spike protein processing and incorporation into progeny virions.PLoS pathogens · 2022Article
- Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health.Human genetics · 2022Review
- Review
- Vav Proteins in Development of the Brain: A Potential Relationship to the Pathogenesis of Congenital Zika Syndrome?Viruses · 2022Review
- Targeting Rac1 for the prevention of atherosclerosis among U.S. Veterans with inflammatory bowel disease.Small GTPases · 2022Article
- Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising "MINT" sequencing strategy and therapeutic "DNA-TG" monitoring.Frontiers in pharmacology · 2022Review
- Advances in Thiopurine Drug Delivery: The Current State-of-the-Art.European journal of drug metabolism and pharmacokinetics · 2021Review
- Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
We have shown recently that the azathioprine metabolite 6-Thio-GTP causes immunosuppression by blockade of GTPase activation in T lymphocytes. In the present study, we describe a new molecular mechanism by which 6-Thio-GTP blocks GTPase activation. Although 6-Thio-GTP could bind to various small GTPases, it specifically blocked activation of Rac1 and Rac2 but not of closely related Rho family members such as Cdc42 and RhoA in primary T cells upon stimulation with alphaCD28 or fibronectin. Binding of 6-Thio-GTP to Rac1 did not suppress Rac effector coupling directly but blocked Vav1 exchange activity upon 6-Thio-GTP hydrolysis, suggesting that 6-Thio-GTP loading leads to accumulation of 6-Thio-GDP-loaded, inactive Rac proteins over time by inhibiting Vav activity. In the absence of apoptosis, blockade of Vav-mediated Rac1 activation led to a blockade of ezrin-radixin-moesin dephosphorylation in primary T cells and suppression of T cell-APC conjugation. Azathioprine-generated 6-Thio-GTP thus prevents the development of an effective immune response via blockade of Vav activity on Rac proteins. These findings provide novel insights into the immunosuppressive effects of azathioprine and suggest that antagonists of the Vav-Rac signaling pathway may be useful for suppression of T cell-dependent pathogenic immune responses.
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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.