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PTPN22 interacts with EB1 to regulate T‐cell receptor signaling
Author(s) -
Zhang Xiaonan,
Yu Yang,
Bai Bin,
Wang Tao,
Zhao Jiahui,
Zhang Na,
Zhao Yanjiao,
Wang Xipeng,
Wang Bing
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902811rr
Subject(s) - ptpn22 , t cell receptor , nfat , protein tyrosine phosphatase , phosphorylation , microbiology and biotechnology , signal transduction , zap70 , biology , t cell , tyrosine phosphorylation , transcription factor , immune system , immunology , gene , biochemistry , genotype , single nucleotide polymorphism
The PTPN22 gene encoding the Lyp/Pep protein tyrosine phosphatase is a negative regulator of T‐cell receptor (TCR) signaling. Recent studies have shown that phosphorylation of end‐binding protein 1 (EB1) is associated with the TCR activation. In this study, using 2‐hybrid and mass spectrometry analyses, we identified EB1 as a protein associated with PTPN22. Furthermore, we discovered that EB1 specifically bound to the P1 domain of PTPN22 by competing with CSK, and the variant PTPN22‐R620W does not affect the association with EB1, which is instrumental with respect to the regulation of TCR signaling. In addition, PTPN22 dephosphorylates EB1 at tyrosine‐247 (Y247), which decreases the expression of the T‐cell activation markers CD25 and CD69 and the phosphorylation levels of the TCR molecules ZAP‐70, LAT, and Erk, leading to the eventual downregulation of the transcription factor NFAT and reduced the levels of secreted IL‐2. The findings of this study provide new insights into the TCR signaling and the T‐cell immune response, which are important for clarifying the mechanism of PTPN22‐related autoimmune diseases.