論文 - 詳細
| RRC ID | 54676 |
|---|---|
| 著者 | Wang X, Li JP, Kuo HK, Chiu LL, Dement GA, Lan JL, Chen DY, Yang CY, Hu H, Tan TH. |
| タイトル | Down-regulation of B cell receptor signaling by hematopoietic progenitor kinase 1 (HPK1)-mediated phosphorylation and ubiquitination of activated B cell linker protein (BLNK). |
| ジャーナル | J Biol Chem |
| Abstract |
Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-like serine/threonine kinase that suppresses immune responses and autoimmunity. B cell receptor (BCR) signaling activates HPK1 by inducing BLNK/HPK1 interaction. Whether HPK1 can reciprocally regulate BLNK during BCR signaling is unknown. Here, we show that HPK1-deficient B cells display hyper-proliferation and hyper-activation of IκB kinase and MAPKs (ERK, p38, and JNK) upon the ligation of BCR. HPK1 attenuates BCR-induced cell activation via inducing BLNK threonine 152 phosphorylation, which mediates BLNK/14-3-3 binding. Furthermore, threonine 152-phosphorylated BLNK is ubiquitinated at lysine residues 37, 38, and 42, leading to attenuation of MAPK and IκB kinase activation in B cells during BCR signaling. These results reveal a novel negative feedback regulation of BCR signaling by HPK1-mediated phosphorylation, ubiquitination, and subsequent degradation of the activated BLNK. |
| 巻・号 | 287(14) |
| ページ | 11037-48 |
| 公開日 | 2012-3-30 |
| DOI | 10.1074/jbc.M111.310946 |
| PII | S0021-9258(20)48036-6 |
| PMID | 22334673 |
| PMC | PMC3322877 |
| MeSH | 14-3-3 Proteins / metabolism Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / metabolism* Animals B-Lymphocytes / cytology B-Lymphocytes / metabolism* Binding Sites Down-Regulation* Enzyme Activation HEK293 Cells Humans Mice Phosphorylation Proteasome Endopeptidase Complex / metabolism Protein Serine-Threonine Kinases / metabolism* Proteolysis Receptors, Antigen, B-Cell / antagonists & inhibitors* Receptors, Antigen, B-Cell / physiology Signal Transduction* Ubiquitination* |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 64 |
| 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 | BLNK^(-) DT40(RCB1510) |