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Essential role of Src-family protein tyrosine kinases in NF- κB activation during B cell development

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Reth,  Michael
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Adachi,  Takahiro
Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Saijo, K., Schmedt, C., Su, I.-h., Karasuyama, H., Lowell, C. A., Reth, M., et al. (2003). Essential role of Src-family protein tyrosine kinases in NF- κB activation during B cell development. Nature Immunology, 4(3), 274-279.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-955A-4
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-κB 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-κB induction. Impaired NF-κB induction was overcome by the activation of protein kinase C (PKC)-λ, thus suggesting the involvement of PKC-λ in pre-BCR-mediated SFK-dependent activation of NF-κB. Our data show the existence of a functionally distinct SFK signaling module responsible for pre-BCR-mediated NF-κB activation and B cell development.