論文 - 詳細
| RRC ID | 42031 |
|---|---|
| 著者 | Spaargaren M, Beuling EA, Rurup ML, Meijer HP, Klok MD, Middendorp S, Hendriks RW, Pals ST. |
| タイトル | The B cell antigen receptor controls integrin activity through Btk and PLCgamma2. |
| ジャーナル | J Exp Med |
| Abstract |
Integrin-mediated adhesion and B cell antigen receptor (BCR) signaling play a critical role in B cell development and function, including antigen-specific B cell differentiation. Here we show that the BCR controls integrin alpha4beta1 (VLA-4)-mediated adhesion of B cells to vascular cell adhesion molecule-1 and fibronectin. Molecular dissection of the underlying signaling mechanism by a combined biochemical, pharmacological, and genetic approach demonstrates that this BCR-controlled integrin-mediated adhesion requires the (consecutive) activation of Lyn, Syk, phosphatidylinositol 3-kinase, Bruton's tyrosine kinase (Btk), phospholipase C (PLC)gamma2, IP3R-mediated Ca2+ release, and PKC. In contrast, activation of mitogen-activated protein kinase kinase (MEK) or extracellular signal-regulated kinase (ERK) is not required, and simultaneous activation of MEK, ERK, and PKB is not sufficient either. Furthermore, Btk is also involved in the control of integrin-mediated adhesion of preB cells. The control of integrin alpha4beta1-mediated B cell adhesion by the BCR involves cytoskeletal reorganization and integrin clustering. These results reveal a novel function for the BCR and Btk, i.e., regulation of integrin alpha4beta1 activity, thereby providing new insights into the control of B cell development and differentiation, as well as into the pathogenesis of the immunodeficiency disease X-linked agammaglobulineamia (XLA). |
| 巻・号 | 198(10) |
| ページ | 1539-50 |
| 公開日 | 2003-11-17 |
| DOI | 10.1084/jem.20011866 |
| PII | jem.20011866 |
| PMID | 14610042 |
| PMC | PMC2194118 |
| MeSH | Agammaglobulinaemia Tyrosine Kinase Agammaglobulinemia / metabolism Animals B-Lymphocytes / metabolism Calcium Calcium-Binding Proteins Cell Adhesion / physiology DNA-Binding Proteins / metabolism Humans Integrins / metabolism* Mice Microfilament Proteins Phosphatidylinositol 3-Kinases / metabolism Phospholipase C gamma Protein Kinase C / metabolism Protein-Tyrosine Kinases / metabolism* Receptors, Antigen, B-Cell / metabolism* Type C Phospholipases / metabolism* Vascular Cell Adhesion Molecule-1 / metabolism |
| IF | 11.743 |
| 引用数 | 134 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL IMMUNOLOGY |
| 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 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | DT40(RCB1464) Syk^(-) DT40(RCB1470) Btk^(-) DT40(RCB1468) PLC-γ2^(-) DT40(RCB1469) |