Faculty Information |
|
Article types | Original article |
Language | English |
Refereed paper | Not refereed |
Title | Protein kinase D regulates positive selection of CD4(+) thymocytes through phosphorylation of SHP-1. |
Journal | Formal name:Nature communications Abbreviation:Nat Commun ISSN code:2041-1723(Electronic)2041-1723(Linking) |
Volume, Number, Page | 7,pp.12756 |
Papers・Author | Ishikawa Eri, Kosako Hidetaka, Yasuda Tomoharu, Ohmuraya Masaki, Araki Kimi, Kurosaki Tomohiro, Saito Takashi, Yamasaki Sho |
Publication date | 2016/09 |
Papers・Description | UNASSIGNED:Thymic selection shapes an appropriate T cell antigen receptor (TCR) repertoire during T cell developUNASSIGNED:ment. 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-1(S557A)) impairs generation of CD4(+) thymocytes. These results suggest that the PKD-SHP-1 axis positively regulates TCR signalling to promote CD4(+) T cell development. |
DOI | 10.1038/ncomms12756 |
PMID | 27670070 |