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- Title
Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production.
- Authors
Gallagher, Ewen; Enzler, Thomas; Matsuzawa, Atsushi; Anzelon-Mills, Amy; Otero, Dennis; Holzer, Ryan; Janssen, Edith; Gao, Min; Karin, Michael
- Abstract
Mice lacking activity of the kinase MEKK1 ('Map3k1ΔKD' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation. Here we show that Map3k1ΔKD mice had defective germinal center formation and diminished production of antibodies recognizing thymus-dependent antigens. Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the kinases Jnk and p38 and transcription factor c-Jun, as well as for expression of cyclin D2 and activation-induced deaminase. MEKK1 was recruited to CD40 and adaptor molecule TRAF2 after CD40 ligation, and Map3k1ΔKD B cells were hypoproliferative after CD40 stimulation. Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production.
- Publication
Nature Immunology, 2007, Vol 8, Issue 1, p57
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1421