論文

査読有り
2008年6月

TCR-induced downregulation of protein tyrosine phosphatase PEST augments secondary T cell responses

MOLECULAR IMMUNOLOGY
  • Yutaka Arimura
  • ,
  • Torkel Vang
  • ,
  • Lutz Tautz
  • ,
  • Scott Williams
  • ,
  • Tomas Mustelin

45
11
開始ページ
3074
終了ページ
3084
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.molimm.2008.03.019
出版者・発行元
PERGAMON-ELSEVIER SCIENCE LTD

We report that the protein tyrosine phosphatase PTP-PEST is expressed in resting human and mouse CD4(+) and CD8(+) T cells, but not in Jurkat T leukemia cells, and that PTP-PEST protein, but not mRNA, was dramatically downregulated in CD4(+) and CD8(+) primary human T cells upon T cell activation. This was also true in mouse CD4(+) T cells, but less striking in mouse CD8+ T cells. PTP-PEST reintroduced into jurkat at levels similar to those in primary human T cells, was a potent inhibitor of TCR-induced transactivation of reporter genes driven by NFAT/AP-1 and NF-kappa B elements and by the entire IL-2 gene promoter. Introduction of PTP-PEST into previously activated primary human T cells also reduced subsequent IL-2 production by these cells in response to TCR and CD28 stimulation. The inhibitory effect of PTP-PEST was associated with dephosphorylation the Lck kinase at its activation loop site (Y394), reduced early TCR-induced tyrosine phosphorylation, reduced ZAP-70 phosphorylation and inhibition of MAP kinase activation. We propose that PTP-PEST tempers T cell activation by dephosphorylating TCR-proximal signaling molecules, such as Lck, and that down-regulation of PTP-PEST may be a reason for the increased response to TCR triggering of previously activated T cells. (C) 2008 Elsevier Ltd. All rights reserved.

Web of Science ® 被引用回数 : 21

リンク情報
DOI
https://doi.org/10.1016/j.molimm.2008.03.019
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/18457880
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000257024800008&DestApp=WOS_CPL

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