Wange Ronald L
Laboratory of Biological Chemistry, Gerontology Research Center, National Institute on Aging, National Institutes of Health, MSC-12, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Mol Interv. 2003 Mar;3(2):75-8, 50. doi: 10.1124/mi.3.2.75.
B lymphocytes and T lymphocytes utilize several proteins with common functions to transduce signals from their respective receptors. However, at the hierarchial signalling level of SLP-76 [Src homology 2(SH2) domain-containing leukocyte protein of 76-kDa] and LAT (linker for activation of T cells) in T cells, the only corresponding protein in B cells was known to be BLNK (B cell linker protein). It was thought that perhaps BLNK performed the cognate roles of SLP-76 and LAT in B cells; however, mounting evidence to the contrary revealed that this hypothesis was not robust. Two laboratories have recently described the characterization of a protein expressed in B cells and myeloid cells, alternatively termed NTAL (non-T cell activation linker) or LAB (linker for activation of B cells). NTAL/LAB and LAT may have arisen from a primordial gene-duplicating event, but genes that code for the two proteins do not share a very high degree of sequence identity. Wange discusses the results of the two reports, the evidence for functional homology between LAT and NTAL/LAB, and the possibility that the differences between them might lead to specific clinical therapeutics to manipulate immune cell responses.
B淋巴细胞和T淋巴细胞利用几种具有共同功能的蛋白质来转导来自各自受体的信号。然而，在T细胞中含Src同源2（SH2）结构域的76 kDa白细胞蛋白（SLP-76）和T细胞活化连接蛋白（LAT）的信号层级水平上，B细胞中唯一对应的蛋白被认为是B细胞连接蛋白（BLNK）。曾有人认为，或许BLNK在B细胞中发挥着与SLP-76和LAT类似的作用；然而，越来越多相反的证据表明这一假设并不成立。最近有两个实验室描述了一种在B细胞和髓样细胞中表达的蛋白质的特性，该蛋白也被称为非T细胞活化连接蛋白（NTAL）或B细胞活化连接蛋白（LAB）。NTAL/LAB和LAT可能源自一次原始的基因复制事件，但编码这两种蛋白质的基因并没有很高的序列同一性。万格讨论了这两篇报告的结果、LAT与NTAL/LAB之间功能同源性的证据，以及它们之间的差异可能导致用于调控免疫细胞反应的特定临床治疗方法的可能性。
