論文 - 詳細
| RRC ID | 39615 |
|---|---|
| 著者 | Petro JB, Rahman SM, Ballard DW, Khan WN. |
| タイトル | Bruton's tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement. |
| ジャーナル | J Exp Med |
| Abstract |
Mutations in the gene encoding Bruton's tyrosine kinase (btk) cause the B cell deficiency diseases X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. In vivo and in vitro studies indicate that the BTK protein is essential for B cell survival, cell cycle progression, and proliferation in response to B cell antigen receptor (BCR) stimulation. BCR stimulation leads to the activation of transcription factor nuclear factor (NF)-kappaB, which in turn regulates genes controlling B cell growth. We now demonstrate that a null mutation in btk known to cause the xid phenotype prevents BCR-induced activation of NF-kappaB. This defect can be rescued by reconstitution with wild-type BTK. This mutation also interferes with BCR-directed activation of IkappaB kinase (IKK), which normally targets the NF-kappaB inhibitor IkappaBalpha for degradation. Taken together, these findings indicate that BTK couples IKK and NF-kappaB to the BCR. Interference with this coupling mechanism may contribute to the B cell deficiencies observed in XLA and xid. |
| 巻・号 | 191(10) |
| ページ | 1745-54 |
| 公開日 | 2000-5-15 |
| DOI | 10.1084/jem.191.10.1745 |
| PMID | 10811867 |
| PMC | PMC2193161 |
| MeSH | Agammaglobulinaemia Tyrosine Kinase Agammaglobulinemia / genetics Agammaglobulinemia / immunology Agammaglobulinemia / metabolism Animals B-Lymphocytes / immunology* B-Lymphocytes / metabolism* Base Sequence Cell Line Chickens DNA Primers / genetics Enzyme Activation Humans I-kappa B Kinase Immunologic Deficiency Syndromes / genetics Immunologic Deficiency Syndromes / immunology Immunologic Deficiency Syndromes / metabolism Mice Mice, Inbred C57BL Mice, Knockout NF-kappa B / metabolism* Protein Serine-Threonine Kinases / metabolism* Protein-Tyrosine Kinases / deficiency Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Receptors, Antigen, B-Cell / metabolism* Signal Transduction |
| IF | 11.743 |
| 引用数 | 242 |
| WOS 分野 | IMMUNOLOGY MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | Btk^(-) DT40(RCB1468) |