Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / deficiency
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / physiology*
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Antigen, B-Cell / physiology*
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Signal Transduction*
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Spleen / metabolism
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bcl-X Protein
Substances
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Bcl2l1 protein, mouse
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NF-kappa B
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, B-Cell
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bcl-X Protein
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt