PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.
PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.
复制标题
SYK 的 PAX5 酪氨酸磷酸化与其丝氨酸磷酸化协同作用，以取消 BLIMP1 的 PAX5 依赖性抑制：抗原触发浆细胞分化的机制。
DOI：
10.1016/j.bbrc.2016.05.067
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kiyoi H
中科院分区：
文献类型：
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作者：
Inagaki Y;Hayakawa F;Hirano D;Kojima Y;Morishita T;Yasuda T;Naoe T;Kiyoi H
浆细胞分化是由B细胞受体(BCR)的抗原刺激启动的，并由BLIMP1调节。在BCR刺激之前，BLIMP1被PAX5抑制，PAX5是维持B细胞特性的关键转录抑制因子。刺激BCR后，BLIMP1上调BLIMP1，进而抑制PAX5。这些事件被认为是触发浆细胞分化的因素；然而，其机制目前尚不清楚。在此，我们证明了BCR信号组件SYK在体外和细胞内引起PAX5酪氨酸磷酸化。PAX5对BLIMP1启动子的转录抑制作用可通过这种磷酸化作用减弱。BCR刺激诱导B细胞SYK磷酸化、PAX5酪氨酸磷酸化和BLIMP1mRNA表达上调。PAX5的酪氨酸磷酸化与PAX5丝氨酸磷酸化通过ERK1/2协同作用，这是我们之前的发现，取消了PAX5依赖的BLIMP1的抑制。这种合作可能是浆细胞分化的触发因素。这些结果表明，PAX5被BCR信号磷酸化是浆细胞分化的初始事件。
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 phosphorylationin vitroand in cells. Transcriptional repression on theBLIMP1promoter 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.