國家衛生研究院 NHRI:Item 3990099045/7762
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/7762
    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7762


    Title: Dual-specificity Phosphatase 14 (DUSP14/MKP6) negatively regulates TCR signaling by inhibiting TAB1 activation
    Authors: Yang, CY;Li, JP;Chiu, LL;Lan, JL;Chen, DY;Chuang, HC;Huang, CY;Tan, TH
    Contributors: Immunology Research Center
    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-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser438, leading to TAB1-TAK1 complex inactivation in T cells. The phosphorylation levels of the TAB1-TAK1 complex and its downstream molecules, including JNK and IkappaB kinase, were enhanced in DUSP14-deficient T cells upon stimulation. The enhanced JNK and IkappaB 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.
    Date: 2014-02-15
    Relation: Journal of Immunology. 2014 Feb 15;192(4):1547-1557.
    Link to: http://dx.doi.org/10.4049/jimmunol.1300989
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000331267200023
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84896729300
    Appears in Collections:[Tse-Hua Tan] Periodical Articles
    [Ching-Yu Huang] Periodical Articles
    [Huai-Chia Chuang] Periodical Articles

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