NDLI: Dual-specificity phosphatase 14 (DUSP14/MKP6) negatively regulates TCR signaling by inhibiting TAB1 activation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chiu, Li-Li Chuang, Huai-Chia Yang, Chia-Yu Lan, Joung-Liang Chen, Der-Yuan Li, Ju-Pi Huang, Ching-Yu Tan, Tse-Hua
Description	Author Affiliation: Yang CY ( Immunology Research Center, National Health Research Institutes, Zhunan 35053, Taiwan)
Abstract	T cell activation is dependent upon phosphorylation of MAPKs, which play a critical role in the regulation of immune responses. Dual-specificity phosphatase 14 (DUSP14; also known as MKP6) is classified as a MAPK phosphatase. The in vivo functions of DUSP14 remain unclear. Thus, we generated DUSP14-deficient mice and characterized the roles of DUSP14 in T cell activation and immune responses. DUSP14 deficiency in T cells resulted in enhanced T cell proliferation and increased cytokine production upon T cell activation. DUSP14 directly interacted with TGF-ß-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser(438), leading to TAB1-TAK1 complex inactivation in T cells. The phosphorylation levels of the TAB1-TAK1 complex and its downstream molecules, including JNK and IκB kinase, were enhanced in DUSP14-deficient T cells upon stimulation. The enhanced JNK and IκB kinase activation in DUSP14-deficient T cells was attenuated by TAB1 short hairpin RNA knockdown. Consistent with that, DUSP14-deficient mice exhibited enhanced immune responses and were more susceptible to experimental autoimmune encephalomyelitis induction. Thus, DUSP14 negatively regulates TCR signaling and immune responses by inhibiting TAB1 activation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Metabolism Dual-specificity Phosphatases Map Kinase Kinase Kinases Receptors, Antigen, T-cell Genetics Animals Cell Differentiation Immunology Cell Proliferation Encephalomyelitis, Autoimmune, Experimental Enzyme Activation I-kappa B Kinase Interferon-gamma Biosynthesis Interleukin-2 Interleukin-4 Jnk Mitogen-activated Protein Kinases Jurkat Cells Lymphocyte Activation Map Kinase Signaling System Mice Mice, Inbred C57bl Mice, Knockout Multiprotein Complexes Phosphorylation Protein Binding Rna Interference Rna, Small Interfering Th1 Cells Th17 Cells Transforming Growth Factor Beta P38 Mitogen-activated Protein Kinases Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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