| First Author | Ishikawa E | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12756 | PubMed ID | 27670070 |
| Mgi Jnum | J:236298 | Mgi Id | MGI:5805710 |
| Doi | 10.1038/ncomms12756 | Citation | Ishikawa E, et al. (2016) Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1. Nat Commun 7:12756 |
| abstractText | Thymic selection shapes an appropriate T cell antigen receptor (TCR) repertoire during T cell development. Here, we show that a serine/threonine kinase, protein kinase D (PKD), is crucial for thymocyte positive selection. In T cell-specific PKD-deficient (PKD2/PKD3 double-deficient) mice, the generation of CD4 single positive thymocytes is abrogated. This defect is likely caused by attenuated TCR signalling during positive selection and incomplete CD4 lineage specification in PKD-deficient thymocytes; however, TCR-proximal tyrosine phosphorylation is not affected. PKD is activated in CD4+CD8+ double positive (DP) thymocytes on stimulation with positively selecting peptides. By phosphoproteomic analysis, we identify SH2-containing protein tyrosine phosphatase-1 (SHP-1) as a direct substrate of PKD. Substitution of wild-type SHP-1 by phosphorylation-defective mutant (SHP-1S557A) impairs generation of CD4+ thymocytes. These results suggest that the PKD-SHP-1 axis positively regulates TCR signalling to promote CD4+ T cell development. |
