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Sci. Signal., 10 August 2010
Vol. 3, Issue 134, p. ra60
[DOI: 10.1126/scisignal.2001104]
RESEARCH ARTICLES
Editor's Summary
Relative Importance
B cell receptor (BCR) signaling drives the development and survival of B cells and their responses to antigens. Members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases mediate BCR signaling. Whereas the p110 isoform of PI3K is necessary for antigen-dependent BCR signaling, its loss does not affect B cell development in the bone marrow. Ramadani et al. found that, whereas deficiency in individual PI3K isoforms in mice did not prevent early B cell development, deficiency in both p110 and p110 blocked antigen-independent, so-called tonic, BCR signaling, which was required for B cell development. In contrast, antigen-dependent signaling required p110. As Limon and Fruman discuss in the accompanying Perspective, the discovery of this role for p110 suggests that the combined inhibition of p110 and p110, rather than of p110 alone, would be more effective as a therapy to target B cell malignancies that involve chronic BCR signaling.
Citation: F. Ramadani, D. J. Bolland, F. Garcon, J. L. Emery, B. Vanhaesebroeck, A. E. Corcoran, K. Okkenhaug, The PI3K Isoforms p110 and p110 Are Essential for Pre–B Cell Receptor Signaling and B Cell Development. Sci. Signal.3, ra60 (2010).
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isoform of PI3K is necessary for antigen-dependent BCR signaling, its loss does not affect B cell development in the bone marrow. Ramadani et al. found that, whereas deficiency in individual PI3K isoforms in mice did not prevent early B cell development, deficiency in both p110
blocked antigen-independent, so-called tonic, BCR signaling, which was required for B cell development. In contrast, antigen-dependent signaling required p110
