The B cell novel protein 1 (BCNP1) regulates BCR signaling and B cell apoptosis
| Autor: | Yang Zhou, Ermeng Xiong, Takeshi Tsubata, Masaki Hikida, Rongjian Hong, Ji-Yang Wang, Yanqing Wang, Yue Tang, Qing Min, Rika Ouchida, Nannan Lai, Jun Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Immunology Receptors Antigen B-Cell Syk Apoptosis Biology Cell Line Mice 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Animals Immunology and Allergy B cell B-Lymphocytes breakpoint cluster region Membrane Proteins Cell biology Pleckstrin homology domain 030104 developmental biology medicine.anatomical_structure biology.protein Phosphorylation GRB2 Signal transduction Apoptosis Regulatory Proteins B-Cell Linker Protein Signal Transduction 030215 immunology |
| Zdroj: | European Journal of Immunology. 49:911-917 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.201847985 |
| Popis: | The BCR plays a central role in B cell development, survival, activation, and differentiation. We have identified the B cell novel protein 1 (BCNP1) as a new regulator of BCR signaling. BCNP1 contains a pleckstrin homology domain, three proline-rich motifs, and a potential SH2 binding site, and is predominantly expressed by B cells. We found that BCNP1 overexpression in WEHI231 immature B cells potentiated α-IgM-induced apoptosis. Conversely, BCNP1-deficient WEHI231 cells, generated by CRISPR-Cas9-mediated genome editing, exhibited reduced apoptosis after BCR crosslinking. Biochemical analyses revealed that BCNP1 physically interacted with the B cell linker protein (BLNK), Grb2, and PLCγ2. Moreover, absence of BCNP1 resulted in accelerated dephosphorylation of BLNK, reduced phosphorylation of SYK and PLCγ2, and decreased Ca2+ influx after BCR crosslinking. These results demonstrate that BCNP1 promotes BCR signaling by modulating the phosphorylation of BLNK, SYK, and PLCγ2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text