title: B-Raf-mediated signaling pathway regulates T cell development.
abstract: The activities of the Raf kinase family proteins control extracellular signal-regulated kinase (ERK) activation in many aspects of cellular responses. However, the relative contributions of individual isozymes to cellular functions including T cell responses are still unclear. In addition to Raf-1, another Raf family kinase, B-Raf, is expressed in murine thymocytes and peripheral T cells, and its activation was induced by TCR stimulation. Here, we investigated the function of B-Raf in development of T cells by generating chimeric mice in which a T cell-compromised host was reconstituted with fetal liver-derived cells from embryonic lethal B-Raf-deficient mice. Although B-Raf was dispensable for normal T cell lineage differentiation at the CD4(-)CD8(-) double-negative stage, thymocytes in the chimeric mice derived from B-Raf(-/-) cells exhibited a drastic arrest of differentiation at the CD4(+)CD8(+) double-positive stage, suggesting that B-Raf is crucial for T cell development, especially for the transition to CD4(+) and CD8(+) single-positive thymocytes. Regarding intracellular signaling, we found that activation of ERK following TCR stimulation was impaired in the thymocytes from the chimeric mice. In conclusion, we present first evidence for the important role of B-Raf-mediated signaling in T cell development.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Hatzopoulos
authors.forename: Leszek
authors.initials: L
authors.lastname: Wojnowski
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004790:Enzyme Induction / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology
chemical_list: C482119:BRAF protein, human; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases