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Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22
C-Maf plays an important role in regulating cytokine production in T(H) 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 kin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439128/ https://www.ncbi.nlm.nih.gov/pubmed/25993510 http://dx.doi.org/10.1371/journal.pone.0127617 |
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author | 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 Miaw, Shi-Chuen |
author_facet | 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 Miaw, Shi-Chuen |
author_sort | Liu, Chih-Chun |
collection | PubMed |
description | C-Maf plays an important role in regulating cytokine production in T(H) 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 T(H)17 cells. Thus, manipulating tyrosine phosphorylation of c-Maf through its kinases and phosphatases can have significant impact on T(H) cell-mediated immune responses. |
format | Online Article Text |
id | pubmed-4439128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44391282015-05-29 Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 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 Miaw, Shi-Chuen PLoS One Research Article C-Maf plays an important role in regulating cytokine production in T(H) 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 T(H)17 cells. Thus, manipulating tyrosine phosphorylation of c-Maf through its kinases and phosphatases can have significant impact on T(H) cell-mediated immune responses. Public Library of Science 2015-05-20 /pmc/articles/PMC4439128/ /pubmed/25993510 http://dx.doi.org/10.1371/journal.pone.0127617 Text en © 2015 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 Miaw, Shi-Chuen Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title | Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title_full | Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title_fullStr | Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title_full_unstemmed | Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title_short | Reciprocal Regulation of C-Maf Tyrosine Phosphorylation by Tec and Ptpn22 |
title_sort | reciprocal regulation of c-maf tyrosine phosphorylation by tec and ptpn22 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439128/ https://www.ncbi.nlm.nih.gov/pubmed/25993510 http://dx.doi.org/10.1371/journal.pone.0127617 |
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