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Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination
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SYSNO ASEP 0511345 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination Author(s) Lo, W.L. (US)
Shah, N.H. (US)
Rubin, S. A. (US)
Zhang, W. (US)
Horková, Veronika (UMG-J) ORCID
Fallahee, I. R. (US)
Štěpánek, Ondřej (UMG-J) RID, ORCID
Zon, L.I. (US)
Kuriyan, J. (US)
Weiss, A. (US)Number of authors 10 Source Title Nature Immunology. - : Nature Publishing Group - ISSN 1529-2908
Roč. 20, č. 11 (2019), s. 1481-1493Number of pages 13 s. Publication form Online - E Language eng - English Country US - United States Keywords homology 2 domain ; lymphoproliferative disease ; phospholipase c-gamma-1 ; signaling complexes ; self-peptides ; activation ; receptor ; tcr ; linker ; binding Subject RIV EB - Genetics ; Molecular Biology OECD category Immunology R&D Projects GJ19-03435Y GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support UMG-J - RVO:68378050 UT WOS 000492309600018 DOI https://doi.org/10.1038/s41590-019-0502-2 Annotation Self-non-self discrimination is central to T cell-mediated immunity. The kinetic proofreading model can explain T cell antigen receptor (TCR) ligand discrimination, however, the rate-limiting steps have not been identified. Here, we show that tyrosine phosphorylation of the T cell adapter protein LAT at position Y132 is a critical kinetic bottleneck for ligand discrimination. LAT phosphorylation at Y132, mediated by the kinase ZAP-70, leads to the recruitment and activation of phospholipase C-gamma 1 (PLC-gamma 1), an important effector molecule for T cell activation. The slow phosphorylation of Y132, relative to other phosphosites on LAT, is governed by a preceding glycine residue (G131) but can be accelerated by substituting this glycine with aspartate or glutamate. Acceleration of Y132 phosphorylation increases the speed and magnitude of PLC-gamma 1 activation and enhances T cell sensitivity to weaker stimuli, including weak agonists and self-peptides. These observations suggest that the slow phosphorylation of Y132 acts as a proofreading step to facilitate T cell ligand discrimination. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2020 Electronic address https://www.nature.com/articles/s41590-019-0502-2
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