title: The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells.
abstract: Protein kinase C-θ (PKC-θ) is required for activation of the transcription factor NF-κB induced by signaling via the T cell antigen receptor (TCR); however, the direct activator of PKC-θ is unknown. We report that the kinase GLK (MAP4K3) directly activated PKC-θ 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-θ 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-θ, and activation of GLK-PKC-θ-IKK could be used as new diagnostic biomarkers and therapeutic targets for systemic lupus erythematosus.
authors: Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan.
authors: Huai-Chia
authors: HC
authors: Chuang
authors: Joung-Liang
authors: JL
authors: Lan
authors: Der-Yuan
authors: DY
authors: Chen
authors: Chia-Yu
authors: CY
authors: Yang
authors: Yi-Ming
authors: YM
authors: Chen
authors: Ju-Pi
authors: JP
authors: Li
authors: Ching-Yu
authors: CY
authors: Huang
authors: Pao-En
authors: PE
authors: Liu
authors: Xiaohong
authors: X
authors: Wang
authors: Tse-Hua
authors: TH
authors: Tan
mesh_terms: D000328:Adult; D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; C543044:MAP4K3 protein, human; D017346:Protein Serine-Threonine Kinases; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta