TY - JOUR
T1 - PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1
T2 - A mechanism for antigen-triggered plasma cell differentiation
AU - Inagaki, Yuichiro
AU - Hayakawa, Fumihiko
AU - Hirano, Daiki
AU - Kojima, Yuki
AU - Morishita, Takanobu
AU - Yasuda, Takahiko
AU - Naoe, Tomoki
AU - Kiyoi, Hitoshi
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/6/24
Y1 - 2016/6/24
N2 - Plasma cell differentiation is initiated by antigen stimulation of the B cell receptor (BCR) and is regulated by BLIMP1. Prior to the stimulation of BCR, BLIMP1 is suppressed by PAX5, which is a key transcriptional repressor that maintains B cell identity. The upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed after the BCR stimulation. These events are considered to trigger plasma cell differentiation; however, the mechanisms responsible currently remain unclear. We herein demonstrated that the BCR signaling component, SYK, caused PAX5 tyrosine phosphorylation in vitro and in cells. Transcriptional repression on the BLIMP1 promoter by PAX5 was attenuated by this phosphorylation. The BCR stimulation induced the phosphorylation of SYK, tyrosine phosphorylation of PAX5, and up-regulation of BLIMP1 mRNA expression in B cells. The tyrosine phosphorylation of PAX5 co-operatively functioned with PAX5 serine phosphorylation by ERK1/2, which was our previous findings, to cancel the PAX5-dependent repression of BLIMP1. This co-operation may be a trigger for plasma cell differentiation. These results imply that PAX5 phosphorylation by a BCR signal is the initial event in plasma cell differentiation.
AB - Plasma cell differentiation is initiated by antigen stimulation of the B cell receptor (BCR) and is regulated by BLIMP1. Prior to the stimulation of BCR, BLIMP1 is suppressed by PAX5, which is a key transcriptional repressor that maintains B cell identity. The upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed after the BCR stimulation. These events are considered to trigger plasma cell differentiation; however, the mechanisms responsible currently remain unclear. We herein demonstrated that the BCR signaling component, SYK, caused PAX5 tyrosine phosphorylation in vitro and in cells. Transcriptional repression on the BLIMP1 promoter by PAX5 was attenuated by this phosphorylation. The BCR stimulation induced the phosphorylation of SYK, tyrosine phosphorylation of PAX5, and up-regulation of BLIMP1 mRNA expression in B cells. The tyrosine phosphorylation of PAX5 co-operatively functioned with PAX5 serine phosphorylation by ERK1/2, which was our previous findings, to cancel the PAX5-dependent repression of BLIMP1. This co-operation may be a trigger for plasma cell differentiation. These results imply that PAX5 phosphorylation by a BCR signal is the initial event in plasma cell differentiation.
KW - BLIMP1
KW - PAX5
KW - Phosphorylation
KW - Plasma cell differentiation
KW - SYK
UR - http://www.scopus.com/inward/record.url?scp=84971290885&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971290885&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2016.05.067
DO - 10.1016/j.bbrc.2016.05.067
M3 - Article
C2 - 27181361
AN - SCOPUS:84971290885
SN - 0006-291X
VL - 475
SP - 176
EP - 181
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -