A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2.
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 of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions.
Takata
M
M
Department of Oncology and Immunology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA.
Kurosaki
T
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D010738:Type C Phospholipases / Q000378:metabolism*; D019061:src-Family Kinases / Q000502:physiology
D004792:Enzyme Precursors; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D011947:Receptors, Antigen, B-Cell; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium