ArticleMolecular and cellular biology2013
Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 116 citations in OpenAlex.
- Article
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- A post-translational regulatory map of chronic antigen-driven human T cell dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Pervanadate-induced oxidation relieves autoinhibition of the protein tyrosine kinase SRC.Science signaling · 2026Article
- Molecular determinants of differential substrate selection between the Src family kinases Lck and Src.Frontiers in immunology · 2026Article
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
- An electrostatic network with strong connectivity is a phospho-sensor for regulating affinity of Syk-receptor association.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Melatonin Modulates ZAP70 and CD40 Transcripts via Histone Modifications in Canine Ileum Epithelial Cells.Veterinary sciences · 2025Article
- Impacts of rs7528684 (-169T/C) onFrontiers in genetics · 2025Article
- The mechanism of allosteric activation of SYK kinase derived from multiple phospho-ITAM-bound structures.Structure (London, England : 1993) · 2024Article
- The LAT Rheostat as a Regulator of Megakaryocyte Activation.Thrombosis and haemostasis · 2024Article
- Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.Science signaling · 2024Article
- Bayesian metamodeling of early T-cell antigen receptor signaling accounts for its nanoscale activation patterns.Frontiers in immunology · 2024Article
- Protein S-palmitoylation modification: implications in tumor and tumor immune microenvironment.Frontiers in immunology · 2024Review
- Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus.Autoimmunity · 2023Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family.International journal of molecular sciences · 2023Review
- CCDC134 facilitates T cell activation through the regulation of early T cell receptor signaling.Frontiers in immunology · 2023Article
- Optical sensing and control of T cell signaling pathways.Frontiers in physiology · 2023Review
- Combined immunodeficiency caused by pathogenic variants in theFrontiers in immunology · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Serial activation of the tyrosine kinases Lck and ZAP-70 initiates signaling downstream of the T cell receptor. We previously reported the structure of an autoinhibited ZAP-70 variant in which two regulatory tyrosine residues (315 and 319) in the SH2-kinase linker were replaced by phenylalanine. We now present a crystal structure of ZAP-70 in which Tyr 315 and Tyr 319 are not mutated, leading to the recognition of a five-residue sequence register error in the SH2-kinase linker of the original crystallographic model. The revised model identifies distinct roles for these two tyrosines. As seen in a recently reported structure of the related tyrosine kinase Syk, Tyr 315 of ZAP-70 is part of a hydrophobic interface between the regulatory apparatus and the kinase domain, and the integrity of this interface would be lost upon engagement of doubly phosphorylated peptides by the SH2 domains. Tyr 319 is not necessarily dislodged by SH2 engagement, which activates ZAP-70 only ∼5-fold in vitro. In contrast, phosphorylation by Lck activates ZAP-70 ∼100-fold. This difference is due to the ability of Tyr 319 to suppress ZAP-70 activity even when the SH2 domains are dislodged from the kinase domain, providing stringent control of ZAP-70 activity downstream of Lck.
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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.