title: Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development.
abstract: The nature of signals that govern the development of immunoglobulin heavy chain-dependent B cells is largely unknown. Using mice deficient for the B cell-expressed Src-family protein tyrosine kinases (SFKs) Blk, Fyn and Lyn, we show an essential role of these kinases in pre-B cell receptor (pre-BCR)- mediated NF-kappaB activation and B cell development. This signaling defect is SFK specific, as a deficiency in Syk, which controls pre-B cell development, does not affect NF-kappaB induction. Impaired NF-kappaB induction was overcome by the activation of protein kinase C (PKC)-lambda, thus suggesting the involvement of PKC-lambda in pre-BCR-mediated SFK-dependent activation of NF-kappaB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-kappaB activation and B cell development.
authors.affiliation: Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA. saijok@mail.rockefeller.edu
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saijo
authors.forename: Christian
authors.initials: C
authors.lastname: Schmedt
authors.forename: I-Hsin
authors.initials: IH
authors.lastname: Su
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Takahiro
authors.initials: T
authors.lastname: Adachi
authors.forename: Alina
authors.initials: A
authors.lastname: Patke
authors.forename: Angela
authors.initials: A
authors.lastname: Santana
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D019061:src-Family Kinases