THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1 View Full Text


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Article Info

DATE

2017-02-27

AUTHORS

Seeyoung Choi, Claude Warzecha, Ekaterina Zvezdova, Jan Lee, Jérémy Argenty, Renaud Lesourne, L Aravind, Paul E Love

ABSTRACT

THEMIS, a T cell-specific protein with high expression in CD4+CD8+ thymocytes, has a crucial role in positive selection and T cell development. THEMIS lacks defined catalytic domains but contains two tandem repeats of a distinctive module of unknown function (CABIT). Here we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1. This action was mediated by the CABIT modules, which bound to the phosphatase domain of SHP-1 and promoted or stabilized oxidation of SHP-1's catalytic cysteine residue, which inhibited the tyrosine-phosphatase activity of SHP-1. Deletion of SHP-1 alleviated the developmental block in Themis-/- thymocytes. Thus, THEMIS facilitates thymocyte positive selection by enhancing the T cell antigen receptor signaling response to low-affinity ligands. More... »

PAGES

433-441

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ni.3692

    DOI

    http://dx.doi.org/10.1038/ni.3692

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084129196

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28250424


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