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Nat Immunol. 2003 Mar;4(3):280-6. Epub 2003 Feb 3.

PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction.

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Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.


Phosphoinositide-3 kinase (PI3K) is thought to activate the tyrosine kinase Btk. However, through analysis of PI3K-/- and Btk-/- mice, B cell antigen receptor (BCR)-induced activation of Btk in mouse B cells was found to be unaffected by PI3K inhibitors or by a lack of PI3K. Consistent with this observation, PI3K-/- Btk-/- double-deficient mice had more severe defects than either single-mutant mouse. NF-kappaB activation along with Bcl-xL and cyclin D2 induction were severely blocked in both PI3K-/- and Btk-/- single-deficient B cells. Transgenic expression of Bcl-xL restored the development and BCR-induced proliferation of B cells in PI3K-/- mice. Our results indicate that PI3K and Btk have unique roles in proximal BCR signaling and that they have a common target further downstream in the activation of NF-kappaB.

[Indexed for MEDLINE]

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