Abstract:
: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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Hong R,Lai N,Ouchida R,Xiong E,Zhou Y,Min Q,Liu J,Tang Y,Hikida M,Tsubata T,Wang Y,Wang JYdoi
10.1002/eji.201847985subject
Has Abstractpub_date
2019-06-01 00:00:00pages
911-917issue
6eissn
0014-2980issn
1521-4141journal_volume
49pub_type
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