Lysine Acetylation Regulates Bruton’s Tyrosine Kinase in B Cell Activation
Lysine Acetylation Regulates Bruton’s Tyrosine Kinase in B Cell Activation
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DOI：
10.4049/jimmunol.0902324
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发表时间：
2009-12
期刊：
影响因子：
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通讯作者：
Zhijian Liu;A. Mai;Jian Sun
中科院分区：
文献类型：
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作者：
Zhijian Liu;A. Mai;Jian Sun
布鲁顿酪氨酸激酶（Btk）是BCR信号转导所必需的，在B细胞中具有多种功能。虽然Btk已被广泛研究，但赖氨酸乙酰化在Btk调节中的作用尚未报道。在这项研究中，我们表明，BCR交联诱导组蛋白赖氨酸乙酰化的Btk启动子，与组蛋白乙酰转移酶E1A相关的300 kDa蛋白（p300）的基因座显着招聘。这些作用增强Btk启动子活性并增加Btk mRNA和蛋白的表达。与这些结果一致，活化的B细胞在体外和体内显示出增加的p300表达和总组蛋白乙酰转移酶活性，导致整体组蛋白乙酰化。有趣的是，我们发现BCR信号诱导由p300介导的Btk赖氨酸乙酰化。此外，Btk的赖氨酸乙酰化促进其磷酸化。总之，我们的研究结果表明，一种新的调节机制Btk转录，并揭示了以前未被识别的翻译后修饰的Btk蛋白及其与磷酸化在B细胞活化。
Bruton’s tyrosine kinase (Btk) is essential for BCR signal transduction and has diverse functions in B cells. Although Btk has been extensively studied, the role of lysine acetylation in Btk regulation has not been reported. In this study, we show that BCR cross-linking induces histone lysine acetylation at the Btk promoter, correlating with marked recruitment of histone acetyltransferase E1A-associated 300-kDa protein (p300) to the locus. These effects enhance Btk promoter activity and increase the expression of Btk mRNA and protein. Consistent with these results, activated B cells display increased p300 expression and total histone acetyltransferase activity in vitro and in vivo, resulting in global histone acetylation. Interestingly, we found that BCR signaling induces Btk lysine acetylation mediated by p300. Moreover, lysine acetylation of Btk promotes its phosphorylation. Together, our results indicate a novel regulatory mechanism for Btk transcription and reveal a previously unrecognized posttranslational modification of the Btk protein and its association with phosphorylation in B cell activation.