Cheng G, Ye Z S, Baltimore D
Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8152-5. doi: 10.1073/pnas.91.17.8152.
Bruton's tyrosine kinase (Btk) is a recently described B-cell-specific tyrosine kinase. Mutations in this gene lead to human X chromosome-linked agammaglobulinemia and murine X-linked immunodeficiency. Although genetic evidence strongly suggests that Btk plays a crucial role in B-lymphocyte differentiation and activation, its precise mechanism of action remains unknown, primarily because the proteins that it interacts with have not yet been identified. Here, we show that Btk interacts with Src homology 3 domains of Fyn, Lyn, and Hck, protein-tyrosine kinases that get activated upon stimulation of B- and T-cell receptors. These interactions are mediated by two 10-aa motifs in Btk. An analogous site with the same specificity is also present in Itk, the T-cell-specific homologue of Btk. Our data extend the range of interactions mediated by Src homology 3 domains and provide an indication of a link between Btk and established signaling pathways in B lymphocytes.
布鲁顿酪氨酸激酶（Btk）是最近发现的一种B细胞特异性酪氨酸激酶。该基因的突变会导致人类X染色体连锁无丙种球蛋白血症和小鼠X连锁免疫缺陷。尽管遗传学证据有力地表明Btk在B淋巴细胞分化和激活中起关键作用，但其确切作用机制仍不清楚，主要是因为尚未鉴定出与其相互作用的蛋白质。在此，我们表明Btk与Fyn、Lyn和Hck的Src同源3结构域相互作用，这些蛋白酪氨酸激酶在B细胞和T细胞受体受到刺激时被激活。这些相互作用由Btk中的两个10个氨基酸的基序介导。Btk的T细胞特异性同源物Itk中也存在具有相同特异性的类似位点。我们的数据扩展了由Src同源3结构域介导的相互作用范围，并提示了Btk与B淋巴细胞中已确立的信号通路之间的联系。
