title: Regulation of NF-kappaB-dependent T cell activation and development by MEKK3.
abstract: The serine/threonine kinase MEKK3, also known as mitogen-activated protein kinase kinase kinase 3, is a critical activator of the transcription factor NF-kappaB in innate immunity. However, the physiological function of MEKK3 in adaptive immunity is unclear. Here we report that following TCR signaling, MEKK3 positively regulated the kinase, IkappaB kinase, leading to NF-kappaB activation. T cells lacking MEKK3 were defective in TCR-induced and cytokine-induced responses. Furthermore, T cell-specific deletion of MEKK3 resulted in reduced numbers of thymocytes and peripheral T cells. Thus, our results provide genetic evidence that MEKK3 plays a crucial role in adaptive immunity.
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Shinohara
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Shiori
authors.initials: S
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000276:immunology / Q000378:metabolism*; D007110:Immunity, Active; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D048748:MAP Kinase Kinase Kinase 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D015851:Interleukin-7; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D051550:I-kappa B Kinase; D048748:MAP Kinase Kinase Kinase 3; C482626:Map3k3 protein, mouse