Abstract
Bruton's tyrosine kinase (BTK) is a member of the SRC-related TEC family of protein tyrosine kinases (PTKs). DT-40 lymphoma B cells, rendered BTK-deficient through targeted disruption of the btk gene by homologous recombination knockout, did not undergo radiation-induced apoptosis, but cells with disrupted lyn or syk genes did. Introduction of the wild-type, or a SRC homology 2 domain or a plecstrin homology domain mutant (but not a kinase domain mutant), human btk gene into BTK-deficient cells restored the apoptotic response to radiation. Thus, BTK is the PTK responsible for triggering radiation-induced apoptosis of lymphoma B cells, and its kinase domain is indispensable for the apoptotic response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Agammaglobulinaemia Tyrosine Kinase
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Animals
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Apoptosis*
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B-Lymphocytes / cytology
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B-Lymphocytes / enzymology
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B-Lymphocytes / radiation effects*
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Chickens
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Gamma Rays
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Gene Targeting
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Humans
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Immunoglobulin M / immunology
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Lymphoma, B-Cell / enzymology
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Lymphoma, B-Cell / pathology*
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Phosphorylation
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / physiology
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Tumor Cells, Cultured
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src Homology Domains
Substances
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Immunoglobulin M
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Receptors, Antigen, B-Cell
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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BTK protein, human