| First Author | Chuang HC | Year | 2011 |
| Journal | Nat Immunol | Volume | 12 |
| Issue | 11 | Pages | 1113-8 |
| PubMed ID | 21983831 | Mgi Jnum | J:177642 |
| Mgi Id | MGI:5295782 | Doi | 10.1038/ni.2121 |
| Citation | Chuang HC, et al. (2011) The kinase GLK controls autoimmunity and NF-kappaB signaling by activating the kinase PKC-theta in T cells. Nat Immunol 12(11):1113-8 |
| abstractText | Protein kinase C-theta (PKC-theta) is required for activation of the transcription factor NF-kappaB 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. |
