期刊
NATURE IMMUNOLOGY
卷 12, 期 11, 页码 1113-U121出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2121
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- National Health Research Institutes of Taiwan [98A1-IMPP01-014]
- Taichung Veterans General Hospital of Taiwan [TCVGH-NHRI01]
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.
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