Dual specificity phosphatase16 is a negative regulator of c-Jun NH2-terminal kinase activity in T cells.
Activation of MAPK is negatively regulated by DUSP, which dephosphorylate the phosphothreonine and phosphotyrosine residues. We have identified a novel JNK-specific DUSP, DUSP16, from murine macrophages. Its involvement in T cells has not yet been defined. In the present study, we found expression of DUSP16 in thymocytes and activated T cells but not in naive T cells. To elucidate the roles of DUSP16 in T cells, transgenic mice expressing a dominant negative form of DUSP16 specifically in T cells were generated (dnDUSP16 Tg). JNK activity was selectively augmented in the thymocytes of these dnDUSP16 Tg mice. CD4 T cells in dnDUSP16 Tg mice showed normal levels of proliferation and IL-2 production after TCR triggering, while they produced increased IFN-gamma but reduced Th2 cytokines compared with wild type CD4 T cells. On the other hand CD8 T cells in dnDUSP16 Tg mice produced an increased amount of IL-2, which resulted in enhanced proliferation and IFN-gamma production. These results suggest that DUSP16 is an important regulator of JNK activity and effector functions of CD4 and CD8 T cells.
Kumabe
Shino
S
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Itsumi
Momoe
M
Yamada
Hisakata
H
Yajima
Toshiki
T
Matsuguchi
Tetsuya
T
Yoshikai
Yasunobu
Y
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*
D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D054639:Mitogen-Activated Protein Kinase Phosphatases; D054637:Dual-Specificity Phosphatases; C438002:Dusp16 protein, mouse