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ID 112446
著者
Ishikawa, Eri Kyushu University
Yasuda, Tomoharu RIKEN
Ohmuraya, Masaki Kumamoto University
Araki, Kimi Kumamoto University
Kurosaki, Tomohiro RIKEN|Osaka University
Satio, Takashi RIKEN|Osaka University
Yamasaki, Sho Kyushu University
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
7
開始ページ
12756
発行日
2016-09-27
備考
Supplementary Figures : ncomms_7_12756_s1.pdf
Supplementary Data : ncomms_7_12756_s2.xls, ncomms_7_12756_s3.xls, ncomms_7_12756_s4.xls
権利情報
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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言語
eng
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部局
先端酵素学研究所