Islam K B, Rabbani H, Larsson C, Sanders R, Smith C I
Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.
J Immunol. 1995 Feb 1;154(3):1265-72.
Triggering of Ag receptors on lymphocytes induces rapid phosphorylation of several receptor-associated protein tyrosine kinases (PTKs), implicating their role in controlling cellular growth and differentiation. In this study, we report the cloning of a human cDNA encoding a nonreceptor PTK with a calculated M(r) of about 58 kDa. The kinase has an overall amino acid identity of approximately 87% with the murine Blk. However, in the unique domain there is only 58% homology and an insertion of six amino acids in the N-terminal region. The nature of this insertion suggests a functional role in membrane attachment. Northern blot analysis showed expression in all stages of B cell development and in T cell lines. The message was not observed in the nonlymphoid tissues examined. In contrast, expression of murine blk in plasma cells and T lymphocytes has not been reported. Importantly, transcripts were seen in human embryonic liver as early as 7.5 wk of gestation before the rearrangement of Ig H chain locus. Furthermore, transcripts were detected in human thymocytes and not in mature T cells. Southern blot analysis revealed polymorphism of this gene in a Caucasian population but not in a Gambian population, indicating a recent origin of this polymorphism. The gene was localized to chromosome 8p22-23. The homology at the protein level suggests that this kinase may be the human homologue of murine Blk. Expression of BLK in immature T cells suggests that BLK may play an important role in thymopoiesis.
淋巴细胞上的抗原受体被激活会诱导几种与受体相关的蛋白酪氨酸激酶（PTK）迅速磷酸化，这表明它们在控制细胞生长和分化中发挥作用。在本研究中，我们报告了一个编码非受体PTK的人类cDNA的克隆，其计算分子量约为58 kDa。该激酶与小鼠Blk的整体氨基酸同一性约为87%。然而，在独特结构域中，同源性仅为58%，且在N端区域有六个氨基酸的插入。这种插入的性质表明其在膜附着中具有功能作用。Northern印迹分析显示其在B细胞发育的所有阶段以及T细胞系中均有表达。在所检测的非淋巴组织中未观察到该信息。相比之下，尚未报道小鼠blk在浆细胞和T淋巴细胞中的表达。重要的是，早在妊娠7.5周Ig H链基因座重排之前，就在人类胚胎肝脏中检测到了转录本。此外，在人类胸腺细胞中检测到了转录本，而在成熟T细胞中未检测到。Southern印迹分析揭示了该基因在高加索人群中有多态性，而在冈比亚人群中没有，这表明这种多态性是最近产生的。该基因定位于染色体8p22 - 23。蛋白质水平的同源性表明该激酶可能是小鼠Blk的人类同源物。BLK在未成熟T细胞中的表达表明BLK可能在胸腺细胞生成中发挥重要作用。
