Bruton's tyrosine kinase (Btk) enhances transcriptional co-activation activity of BAM11, a Btk-associated molecule of a subunit of SWI/SNF complexes
Bruton's tyrosine kinase (Btk) enhances transcriptional co-activation activity of BAM11, a Btk-associated molecule of a subunit of SWI/SNF complexes
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DOI：
10.1093/intimm/dxh076
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Takatsu, K
中科院分区：
文献类型：
--
作者：
Hirano, M;Kikuchi, Y;Takatsu, K
Bruton‘s酪氨酸激酶(BTK)是B细胞发育和细胞表面分子如BCR和IL-5受体信号转导所必需的。我们已经确定了BTK相关分子BAM11(以下简称BAM)，它与BTK的Pleckstrin同源(PH)结构域结合，在体内和体外都能抑制BTK的活性。在这项研究中，我们证明了BAM的转录共激活活性及其与BTK的功能相互作用。通过瞬时转录实验，我们证明了BAM的强制表达增强了合成报告基因的转录活性。BAM的C末端对于转录共激活活性是必不可少的。BTK和BAM的异位表达增强了BAM的转录共激活活性。BAM的转录共激活活性通过与BTK的相互作用而增强，并且需要其完整的PH结构域和功能激酶活性。我们还发现，另一种具有转录活性的BTK结合蛋白TFII-I的强制表达，与BAM和BTK一起，进一步增强了BAM和BTK依赖的转录共激活。此外，BAM可以与INI1/SNF5蛋白共沉淀，INI1/SNF5蛋白是SWI/SNF复合体的成员，它重塑染色质并激活转录。我们提出了一个模型，在该模型中，BTK通过激活BAM和通过TFII-I激活SWI/SNF转录复合体来调节B细胞中的基因转录。
Bruton's tyrosine kinase (Btk) is required for B cell development and signal transduction through cell-surface molecules such as BCR and IL-5 receptor. We have identified a Btk-associated molecule, BAM11 (hereafter referred to as BAM) that binds to the pleckstrin homology (PH) domain of Btk, and inhibits Btk activity both in vivo and in vitro. In this study, we demonstrate BAM's transcriptional co-activation activity and its functional interaction with Btk. By using transient transcription assays, we demonstrate that the enforced expression of BAM enhances transcriptional activity of the synthetic reporter gene. The C-terminus of BAM is essential for the transcriptional co-activation activity. The ectopic expression of Btk together with BAM enhances BAM's transcriptional co-activation activity. BAM's transcriptional co-activation activity is enhanced through interaction with Btk, and requires both its intact PH domain and functional kinase activity. We also show that enforced expression of TFII-I, another Btk-binding protein with transcriptional activity, together with BAM and Btk, further augments BAM- and Btk-dependent transcriptional co-activation. Furthermore, BAM can be co-immunoprecipitated with the INI1/SNF5 protein, a member of the SWI/SNF complex that remodels chromatin and activates transcription. We propose a model in which Btk regulates gene transcription in B cells by activating BAM and the SWI/SNF transcriptional complex via TFII-I activation.