title: THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1.
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.
authors.affiliation: Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Seeyoung
authors.initials: S
authors.lastname: Choi
authors.affiliation: Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Claude
authors.initials: C
authors.lastname: Warzecha
authors.affiliation: Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Zvezdova
authors.affiliation: Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale, U1043, Centre National de la Recherche Scientifique, U5282, and Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Argenty
authors.affiliation: Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.|Institut National de la Santé et de la Recherche Médicale, U1043, Centre National de la Recherche Scientifique, U5282, and Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lesourne
authors.affiliation: National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: L
authors.initials: L
authors.lastname: Aravind
authors.affiliation: Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Love
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D060966:Clonal Selection, Antigen-Mediated / Q000276:immunology*; D017353:Gene Deletion; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; C557796:thymocyte-expressed molecule involved in selection, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6