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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
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Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development

Kaoru Saijo1, Christian Schmedt, I-Hsin Su

  • 1Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA. saijok@mail.rockefeller.edu

Nature Immunology
|February 4, 2003
PubMed

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.

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