ArticleScience signaling2013
Activation loop dynamics determine the different catalytic efficiencies of B cell- and T cell-specific tec kinases.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 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
- More than an attachment module: covalent inhibitor warheads influence BTK dynamics and function.bioRxiv : the preprint server for biology · 2026Article
- Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines.Science signaling · 2025Article
- In BTK, phosphorylated Y223 in the SH3 domain mirrors catalytic activity, but does not influence biological function.Blood advances · 2024Article
- Article
- Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.PloS one · 2023Article
- Differences in the dynamics of the tandem-SH2 modules of the Syk and ZAP-70 tyrosine kinases.Protein science : a publication of the Protein Society · 2021Article
- A mechanism for localized dynamics-driven activation in Bruton's tyrosine kinase.Royal Society open science · 2021Article
- Atypical Presentation of Severe Fungal Necrotizing Fasciitis in a Patient with X-Linked Agammaglobulinemia.Journal of clinical immunology · 2021Article
- Visualization of Host Cell Kinase Activation by Viral Proteins Using GFP Fluorescence Complementation and Immunofluorescence Microscopy.Bio-protocol · 2021Article
- Reining in BTK: Interdomain Interactions and Their Importance in the Regulatory Control of BTK.Frontiers in cell and developmental biology · 2021Review
- Comparison of tyrosine kinase domain properties for the neurotrophin receptors TrkA and TrkB.The Biochemical journal · 2020Article
- Lipid-targeting pleckstrin homology domain turns its autoinhibitory face toward the TEC kinases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Dynamic regulatory features of the protein tyrosine kinases.Biochemical Society transactions · 2019Review
- MgThe Journal of experimental medicine · 2019Article
- The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases.Critical reviews in biochemistry and molecular biology · 2018Review
- Protein kinase Cα gain-of-function variant in Alzheimer's disease displays enhanced catalysis by a mechanism that evades down-regulation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Subzero Celsius separations in three-zone temperature controlled hydrogen deuterium exchange mass spectrometry.Journal of chromatography. A · 2017Article
- An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.Biochemistry · 2017Article
- Paralog-Specific Patterns of Structural Disorder and Phosphorylation in the Vertebrate SH3-SH2-Tyrosine Kinase Protein Family.Genome biology and evolution · 2016Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Itk (interleukin-2-inducible T cell kinase) and Btk (Bruton's tyrosine kinase) are nonreceptor tyrosine kinases of the Tec family that signal downstream of the T cell receptor (TCR) and B cell receptor (BCR), respectively. Despite their high sequence similarity and related signaling roles, Btk is a substantially more active kinase than Itk. We showed that substitution of 6 of the 619 amino acid residues of Itk with the corresponding residues of Btk (and vice versa) was sufficient to completely switch the activities of Itk and Btk. The substitutions responsible for the swap in activity are all localized to the activation segment of the kinase domain. Nuclear magnetic resonance and hydrogen-deuterium exchange mass spectrometry analyses revealed that Itk and Btk had distinct protein dynamics in this region, which could explain the differences in catalytic efficiency between these kinases. Introducing Itk with enhanced activity into T cells led to enhanced and prolonged TCR signaling compared to that in cells with wild-type Itk. These findings imply that evolutionary pressures have led to Tec kinases having distinct enzymatic properties, depending on the cellular context. We suggest that the weaker catalytic activities of T cell-specific kinases serve to regulate cellular activation and prevent aberrant immune responses.
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