title: The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and effector function in CD8(+) T cells.
abstract: Signals from the T-cell recognition of antigen program effector functions are necessary to clear infections and tumors. The JNK pathway is critically important in regulating this process. In T lymphocytes, JNK1 and JNK2 have distinct functions depending on their maturation state and cell-type. However, the mechanisms that regulate their isoform-specific activity and function are still unclear. Here, we identify plenty of SH3 (POSH) and JNK-interacting protein 1 (JIP-1) as a multiprotein scaffold network for TCR-mediated JNK1 activation in CD8(+) T cells. Disruption of the POSH/JIP-1 complex led to profound defects in the activation of JNK1, as well as deficient activation or induction of the transcription factors c-Jun, T-bet, and Eomesodermin. Furthermore, disruption of the POSH/JIP complex in CD8(+) T cells resulted in impaired proliferation, decreased cytokine expression, and the inability to control tumors. Collectively, these data identify a mechanism for the specific regulation of TCR-dependent JNK1 activation and function that is key for CD8(+) T-cell responses.
authors: Department of Molecular Microbiology and Immunology & Department of Surgery, Center for Cellular and Molecular Immunology, School of Medicine, University of Missouri, Columbia, MO, USA.
authors: Cody A
authors: CA
authors: Cunningham
authors: Karin M
authors: KM
authors: Knudson
authors: Binghao J
authors: BJ
authors: Peng
authors: Emma
authors: E
authors: Teixeiro
authors: Mark A
authors: MA
authors: Daniels
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D003598:Cytoskeletal Proteins; C491198:Eomes protein, mouse; C490665:Mapk8ip protein, mouse; C111370:Sh3md2 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D048055:Mitogen-Activated Protein Kinase 8
keywords: CD8+ T cells; Immune responses; Molecular immunology; Signal transduction