Reciprocal regulation of C-Maf tyrosine phosphorylation by Tec and Ptpn22
Journal
PloS one
Journal Volume
10
Journal Issue
5
Date Issued
2015
Author(s)
Liu, Chih-Chun
Lai, Chen-Yen
Yen, Wei-Feng
Lin, Yu-Hsien
Chang, Hui-Hsin
Tai, Tzong-Shyuan
Lu, Yu-Jung
Tsao, Hsiao-Wei
Ho, I-Cheng
Abstract
C-Maf plays an important role in regulating cytokine production in TH cells. Its transactivation of IL-4 is optimized by phosphorylation at Tyr21, Tyr92, and Tyr131. However, the molecular mechanism regulating its tyrosine phosphorylation remains unknown. In this study, we demonstrate that Tec kinase family member Tec, but not Rlk or Itk, is a tyrosine kinase of c-Maf and that Tec enhances c-Maf-dependent IL-4 promoter activity. This effect of Tec is counteracted by Ptpn22, which physically interacts with and facilitates tyrosine dephosphorylation of c-Maf thereby attenuating its transcriptional activity. We further show that phosphorylation of Tyr21/92/131 of c-Maf is also critical for its recruitment to the IL-21 promoter and optimal production of this cytokine by TH17 cells. Thus, manipulating tyrosine phosphorylation of c-Maf through its kinases and phosphatases can have significant impact on TH cell-mediated immune responses.
SDGs
Publisher
PUBLIC LIBRARY SCIENCE
Type
journal article