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

Nature immunology | 2017

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.

Pubmed ID: 28250424 RIS Download

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Associated grants

  • Agency: Intramural NIH HHS, United States
    Id: Z01 HD001803-14
  • Agency: Intramural NIH HHS, United States
    Id: Z01 HD001803-15
  • Agency: Intramural NIH HHS, United States
    Id: Z99 HD999999
  • Agency: Intramural NIH HHS, United States
    Id: ZIA HD001803

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ImaGene (tool)

RRID:SCR_002178

Software tool as convolutional neural network to quantify natural selection from genomic data.Supervised machine learning algorithm to predict natural selection and estimate selection coefficients from population genomic data. Can be used to estimate any parameter of interest from evolutionary population genetics model.

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions