| First Author | Choi S | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 4 | Pages | 433-441 |
| PubMed ID | 28250424 | Mgi Jnum | J:258683 |
| Mgi Id | MGI:6140594 | Doi | 10.1038/ni.3692 |
| Citation | Choi S, et al. (2017) THEMIS enhances TCR signaling and enables positive selection by selective inhibition of the phosphatase SHP-1. Nat Immunol 18(4):433-441 |
| abstractText | 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. |
