title: POSH Regulates CD4+ T Cell Differentiation and Survival.
abstract: The scaffold molecule POSH is crucial for the regulation of proliferation and effector function in CD8(+) T cells. However, its role in CD4(+) T cells is not known. In this study, we found that disruption of the POSH scaffold complex established a transcriptional profile that strongly skewed differentiation toward Th2, led to decreased survival, and had no effect on cell cycle entry. This is in stark contrast to CD8(+) T cells in which POSH regulates cell cycle and does not affect survival. Disruption of POSH in CD4(+) T cells resulted in the loss of Tak1-dependent activation of JNK1/2 and Tak1-mediated survival. However, in CD8(+) T cells, POSH regulates only JNK1. Remarkably, each type of T cell had a unique composition of the POSH scaffold complex and distinct posttranslational modifications of POSH. These data indicate that the mechanism that regulates POSH function in CD4(+) T cells is different from CD8(+) T cells. All together, these data strongly suggest that POSH is essential for the integration of cell-type-specific signals that regulate the differentiation, survival, and function of T cells.
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Cody A
authors.identifier: 0000-0002-6507-3804
authors.initials: CA
authors.lastname: Cunningham
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Leah N
authors.initials: LN
authors.lastname: Cardwell
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212.
authors.forename: Emma
authors.initials: E
authors.lastname: Teixeiro
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212 danielsma@missouri.edu.
authors.forename: Mark A
authors.identifier: 0000-0002-5175-9901
authors.initials: MA
authors.lastname: Daniels
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D058408:Th1-Th2 Balance; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D020930:MAP Kinase Kinase Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D000099151:MAP Kinase Kinase Kinase 7; C111370:Sh3md2 protein, mouse