共 24 条
The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells
被引:121
作者:

Chuang, Huai-Chia
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h-index: 0
机构:
Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Lan, Joung-Liang
论文数: 0 引用数: 0
h-index: 0
机构:
Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung, Taiwan
Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Chen, Der-Yuan
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h-index: 0
机构:
Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung, Taiwan
Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Yang, Chia-Yu
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机构:
Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Chen, Yi-Ming
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h-index: 0
机构:
Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung, Taiwan
Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Li, Ju-Pi
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机构:
Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Huang, Ching-Yu
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h-index: 0
机构:
Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Liu, Pao-En
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h-index: 0
机构:
Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung, Taiwan Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Wang, Xiaohong
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h-index: 0
机构:
Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan

Tan, Tse-Hua
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h-index: 0
机构:
Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan
Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan
机构:
[1] Natl Hlth Res Inst, Immunol Res Ctr, Zhunan, Taiwan
[2] Taichung Vet Gen Hosp, Div Allergy Immunol & Rheumatol, Taichung, Taiwan
[3] Natl Yang Ming Univ, Fac Med, Taipei 112, Taiwan
[4] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA
关键词:
C-THETA;
DIFFERENTIAL REQUIREMENT;
DEFICIENT MICE;
ENCEPHALOMYELITIS;
RECRUITMENT;
RECEPTOR;
PATHWAY;
COMPLEX;
CARMA1;
DEPEND;
D O I:
10.1038/ni.2121
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Protein kinase C-theta (PKC-theta) is required for activation of the transcription factor NF-kappa B induced by signaling via the T cell antigen receptor (TCR); however, the direct activator of PKC-theta is unknown. We report that the kinase GLK (MAP4K3) directly activated PKC-theta during TCR signaling. TCR signaling activated GLK by inducing its direct interaction with the upstream adaptor SLP-76. GLK-deficient mice had impaired immune responses and were resistant to experimental autoimmune encephalomyelitis. Consistent with that, people with systemic lupus erythematosus had considerable enhanced GLK expression and activation of PKC-theta and the kinase IKK in T cells, and the frequency of GLK-overexpressing T cells was directly correlated with disease severity. Thus, GLK is a direct activator of PKC-theta, and activation of GLK-PKC-theta-IKK could be used as new diagnostic biomarkers and therapeutic targets for systemic lupus erythematosus.
引用
收藏
页码:1113 / U121
页数:7
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机构: NIA, Ctr Gerontol Res, Biol Chem Lab, NIH, Baltimore, MD 21224 USA