A Role for Bruton's Tyrosine Kinase in B Cell Antigen
نویسنده
چکیده
Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling o fDT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)--~/2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCK-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-~/2 activation. Since Syk is also required for the BCK-induced PLC-~/2 activation, our findings indicate that PLC-~/2 activation is regulated by Btk and Syk through their concerted actions.
منابع مشابه
Deficient Expression of Bruton's Tyrosine Kinase in Monocytes from X-Linked Agammaglobulinemia as Evaluated by a Flow Cytometric Analysis and its Clinical Application to Carrier Detection
Background: The B-cell defect in X-linked agammaglobulinemia (XLA) is caused by mutations in the gene for Bruton's tyrosine kinase (BTK). BTK mutations result in deficient expression of BTK protein in peripheral blood monocytes. Methods: Using the anti-BTK monoclonal antibody (48-2H), a flow cytometric analysis of intra cytoplasmic BTK protein expression in monocytes was performed to identify I...
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Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR sign...
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