ArticleNature immunology2011
The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells.
Article in Nature immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 141 citations in OpenAlex.
- HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results.Cell reports. Medicine · 2026Trial
- From inhibition to degradation: advances in highly selective targeting strategies for HPK1.Molecular diversity · 2026Review
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Genetic and functional insights into long noncoding RNAs in schizophrenia.Molecular psychiatry · 2026Article
- MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.The Journal of clinical investigation · 2026Article
- Benchmarking EGF signaling pathway inference using phosphoproteomics and kinase-substrate interactions.Nature communications · 2026Article
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- The NF-κB signaling network in the life of T cells.Frontiers in immunology · 2025Review
- DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-mediated allergic inflammation by promoting nuclear export of Pur-α.The Journal of clinical investigation · 2023Article
- ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification.Journal of biomedical science · 2023Review
- MAP4K3 inhibits Sirtuin-1 to repress the LKB1-AMPK pathway to promote amino acid-dependent activation of the mTORC1 complex.Life science alliance · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- The Peptidyl-ProlylFrontiers in immunology · 2023Article
- Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis.Frontiers in immunology · 2023Article
- NFκB signaling in T cell memory.Frontiers in immunology · 2023Review
- SARS-CoV-2 spike protein enhances MAP4K3/GLK-induced ACE2 stability in COVID-19.EMBO molecular medicine · 2022Article
- Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus.Annals of the rheumatic diseases · 2022Article
- Targeting Indoleamine Dioxygenase and Tryptophan Dioxygenase in Cancer Immunotherapy: Clinical Progress and Challenges.Drug design, development and therapy · 2022Review
- MAP4K3/GLK inhibits Treg differentiation by direct phosphorylating IKKβ and inducing IKKβ-mediated FoxO1 nuclear export and Foxp3 downregulation.Theranostics · 2022Article
- Induction of Interferon-γ and Tissue Inflammation by Overexpression of Eosinophil Cationic Protein in T Cells and Exosomes.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.