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Publication : Reciprocal regulation of C-Maf tyrosine phosphorylation by Tec and Ptpn22.

First Author  Liu CC Year  2015
Journal  PLoS One Volume  10
Issue  5 Pages  e0127617
PubMed ID  25993510 Mgi Jnum  J:235414
Mgi Id  MGI:5796251 Doi  10.1371/journal.pone.0127617
Citation  Liu CC, et al. (2015) Reciprocal regulation of C-Maf tyrosine phosphorylation by Tec and Ptpn22. PLoS One 10(5):e0127617
abstractText  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.
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