Tyrosine phosphorylation of c-Maf enhances the expression of IL-4 gene.
Maf proteins are involved in a variety of biological processes, such as oncogenesis, lens development, and differentiation. In immune system, c-Maf transactivates IL-4 promoter, and ectopic expression of c-Maf skews primary T cell response toward the Th2 pathway. Numerous transcription factors are subjected to posttranslational modification. In this study, to our knowledge, we show for the first time that c-Maf is subjective to tyrosine phosphorylation in Th cells and that the level of its tyrosine phosphorylation positively correlates with IL-4 expression by peripheral Th cells, but is negatively associated with the severity of disease in NOD mice. c-Maf undergoes tyrosine phosphorylation at Tyr(21), Tyr(92), and Tyr(131) residues in Th2 cells. Furthermore, tyrosine phosphorylation at these three residues is critical for the recruitment of c-Maf to IL-4 promoter and IL-4 production in Th cells. Taken together, this study sheds new light on the role of posttranslational modification of c-Maf in IL-4 production and Th cell-mediated autoimmune diseases.
Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
Chen-Yen
CY
Lai
Shin-Ying
SY
Lin
Chia-Kai
CK
Wu
Li-Tzu
LT
Yeh
Huey-Kang
HK
Sytwu
Shi-Chuen
SC
Miaw
D000818:Animals; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000378:metabolism*; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D015847:Interleukin-4; D014443:Tyrosine