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

Nature immunology | Mar 26, 2003

http://www.ncbi.nlm.nih.gov/pubmed/12563261

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.

Pubmed ID: 12563261 RIS Download

Mesh terms: Animals | B-Lymphocytes | Cell Differentiation | Mice | Mice, Inbred C57BL | NF-kappa B | src-Family Kinases

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI053545-01
  • Agency: NIDDK NIH HHS, Id: DK58066
  • Agency: NHLBI NIH HHS, Id: HL54476

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