BAP-135，一种布鲁顿酪氨酸激酶在B细胞受体激活时的作用靶点。
BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement.
作者信息
Yang W, Desiderio S
机构信息
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):604-9. doi: 10.1073/pnas.94.2.604.
Abstract
Bruton's tyrosine kinase (Btk) is essential for B cell activation, but downstream targets of Btk have not been defined. We now describe a protein, BAP-135, that is associated with Btk in B cells and is a substrate for phosphorylation by Btk. BAP-135, which exhibits no detectable homology to known proteins, contains six occurrences of a hitherto undescribed amino acid repeat and two motifs, similar to the Src autophosphorylation site, that represent potential targets for tyrosine phosphorylation. The pleckstrin homology domain of Btk comprises the principal site of BAP-135 binding. Btk-dependent phosphorylation of BAP-135 is abolished by mutations that impair activation of Btk by Src-related kinases. Btk and BAP-135 exist in a complex before B cell antigen receptor (BCR) engagement; in response to BCR crosslinking, BAP-135 is transiently phosphorylated on tyrosine. Taken together, these observations suggest that BAP-135 may reside downstream of Btk in a signaling pathway originating at the BCR.
摘要
布鲁顿酪氨酸激酶（Btk）对B细胞活化至关重要，但Btk的下游靶点尚未明确。我们现在描述一种蛋白质BAP - 135，它在B细胞中与Btk相关联，并且是Btk磷酸化的底物。BAP - 135与已知蛋白质没有可检测到的同源性，包含六个迄今未描述的氨基酸重复序列以及两个类似于Src自身磷酸化位点的基序，这些基序代表酪氨酸磷酸化的潜在靶点。Btk的普列克底物蛋白同源结构域是BAP - 135结合的主要位点。损害Src相关激酶对Btk激活的突变会消除Btk依赖的BAP - 135磷酸化。在B细胞抗原受体（BCR）结合之前，Btk和BAP - 135以复合物形式存在；响应BCR交联，BAP - 135在酪氨酸上被短暂磷酸化。综上所述，这些观察结果表明BAP - 135可能在源自BCR的信号通路中位于Btk的下游。
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