ArticleProceedings of the National Academy of Sciences of the United States of America2002
Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 277 citations in OpenAlex.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multidimensional pan-cancer analysis reveals the impact of PPIA on tumor epigenetic modifications and immune regulation.Scientific reports · 2025Article
- Cyclophilin A: promising target in cancer therapy.Cancer biology & therapy · 2024Review
- Genome-wide identification and expression analyses ofPhysiology and molecular biology of plants : an international journal of functional plant biology · 2024Article
- Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers.Molecules (Basel, Switzerland) · 2024Review
- "Cyclophilin A" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis.Current Alzheimer research · 2024Article
- Review
- Article
- Phosphorylation of the prolyl isomerase Cyclophilin A regulates its localisation and release from the centrosome during mitosis.Cell cycle (Georgetown, Tex.) · 2023Article
- Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.Cellular and molecular life sciences : CMLS · 2022Article
- Genome-wide identification and stress response analysis of cyclophilin gene family in apple (Malus × domestica).BMC genomics · 2022Article
- Review
- A Novel Ex Vivo Approach Based on Proteomics and Biomarkers to Evaluate the Effects of Chrysene, MEHP, and PBDE-47 on Loggerhead Sea Turtles (International journal of environmental research and public health · 2022Article
- Cyclophilin anaCyp40 regulates photosystem assembly and phycobilisome association in a cyanobacterium.Nature communications · 2022Article
- Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants.Microbiology spectrum · 2022Article
- Characterization of Cyclophilin from ThaumarchaeotaACS omega · 2022Article
- Diketopiperazine Formation from FPGThe journal of physical chemistry. B · 2021Article
- Cyclophilin A Plays Potential Roles in a Rat Model of Asthma and Suppression of Immune Response.Journal of asthma and allergy · 2021Article
- A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI.Pharmaceuticals (Basel, Switzerland) · 2020Article
- The contribution of cyclophilin A to immune-mediated central nervous system inflammation.Journal of neuroimmunology · 2020Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-2 tyrosine kinase (Itk) is a nonreceptor protein tyrosine kinase of the Tec family that participates in the intracellular signaling events leading to T cell activation. Tec family members contain the conserved SH3, SH2, and catalytic domains common to many kinase families, but they are distinguished by unique sequences outside of this region. The mechanism by which Itk and related Tec kinases are regulated is not well understood. Our studies indicate that Itk catalytic activity is inhibited by the peptidyl prolyl isomerase activity of cyclophilin A (CypA). NMR structural studies combined with mutational analysis show that a proline-dependent conformational switch within the Itk SH2 domain regulates substrate recognition and mediates regulatory interactions with the active site of CypA. CypA and Itk form a stable complex in Jurkat T cells that is disrupted by treatment with cyclosporin A. Moreover, the phosphorylation levels of Itk and a downstream substrate of Itk, PLCgamma1, are increased in Jurkat T cells that have been treated with cyclosporin A. These findings support a novel mode of tyrosine kinase regulation for a Tec family member and provide a molecular basis for understanding a cellular function of the ubiquitous peptidyl prolyl isomerase, CypA.
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Registered trials
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