DEFICIENT EXPRESSION OF A B-CELL CYTOPLASMIC TYROSINE KINASE IN HUMAN X-LINKED AGAMMAGLOBULINEMIA
DEFICIENT EXPRESSION OF A B-CELL CYTOPLASMIC TYROSINE KINASE IN HUMAN X-LINKED AGAMMAGLOBULINEMIA
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DOI：
10.1016/0092-8674(93)90667-f
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发表时间：
1993-01-29
期刊：
影响因子：
64.5
通讯作者：
WITTE, ON
中科院分区：
文献类型：
--
作者：
TSUKADA, S;SAFFRAN, DC;WITTE, ON
我们描述了一种新的胞质酪氨酸激酶，称为BPK（B细胞祖细胞激酶），它在B谱系的所有阶段和髓样细胞中表达。BPK具有经典的SH 1、SH 2和SH 3结构域，但缺乏肉豆蔻酰化信号和对应于c-src的酪氨酸527的调节磷酸化位点。BPK在SH 3结构域上游有一个长的碱性氨基末端区域。BPK被评估为人类X连锁无丙种球蛋白血症（XLA）的候选者，XLA是一种遗传性免疫缺陷，其特征为严重的B和浆细胞缺陷以及严重的低丙种球蛋白血症。BPK映射到探针的100 kb内，该探针定义了与XLA在DXS 178处最紧密连锁的多态性。在XLA前B和B细胞系中观察到BPK mRNA、蛋白表达和激酶活性的减少或缺失。BPK可能是XLA基因，并在细胞扩增的关键途径中发挥作用。
We describe a novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells. BPK has classic SH1, SH2, and SH3 domains, but lacks myristylation signals and a regulatory phosphorylation site corresponding to tyrosine 527 of c-src. BPK has a long, basic amino-terminal region upstream of the SH3 domain. BPK was evaluated as a candidate for human X-linked agammaglobulinemia (XLA), an inherited immunodeficiency characterized by a severe deficit of B and plasma cells and profound hypogammaglobulinemia. BPK mapped to within 100 kb of a probe defining the polymorphism most closely linked to XLA at DXS178. Reduction in or the absence of BPK mRNA, protein expression, and kinase activity was observed in XLA pre-B and B cell lines. BPK is likely the XLA gene and functions in pathways critical to 8 cell expansion.