Lelias J M, Adra C N, Wulf G M, Guillemot J C, Khagad M, Caput D, Lim B
Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1479-83. doi: 10.1073/pnas.90.4.1479.
We have identified the mRNA for a human gene, denoted D4, which is expressed at very high levels in hematopoietic cell lines and in normal cells of lymphoid and myeloid origin. The 1.5-kb transcript is absent or detectable only at low levels in nonhematopoietic tissues. D4 encodes a 201-amino acid protein with homology to rhoGDI, an inhibitor of GDP dissociation for the ras-homologous protein rho. D4 might function also as a regulator of guanine nucleotide exchange for small GTP-binding proteins. A homologous transcript of similar size is also preferentially expressed in murine hematopoietic tissues. When totipotent murine embryonic stem cells develop in vitro into hematopoietic cells, the gene is activated with the onset of hematopoiesis. When hematopoietic cell lines are induced to differentiate, the expression of D4 is modulated. Thus, D4 appears to be a developmentally regulated gene. Its preferential expression in hematopoietic cells indicates that D4 likely plays some significant role in the growth and differentiation processes of hematopoietic cells. This significance is underscored by increasing evidence for the involvement of regulators of G proteins in clinical diseases.
我们已经鉴定出一种人类基因的信使核糖核酸（mRNA），命名为D4，它在造血细胞系以及淋巴系和髓系来源的正常细胞中高水平表达。在非造血组织中，这种1.5千碱基的转录本不存在或仅能低水平检测到。D4编码一种含201个氨基酸的蛋白质，与rhoGDI具有同源性，rhoGDI是一种针对ras同源蛋白rho的GDP解离抑制剂。D4可能还作为小GTP结合蛋白鸟嘌呤核苷酸交换的调节剂发挥作用。一个大小相似的同源转录本也在小鼠造血组织中优先表达。当全能性小鼠胚胎干细胞在体外发育成造血细胞时，该基因随着造血作用的开始而被激活。当诱导造血细胞系分化时，D4的表达受到调控。因此，D4似乎是一个受发育调控的基因。它在造血细胞中的优先表达表明D4可能在造血细胞的生长和分化过程中发挥某种重要作用。G蛋白调节剂参与临床疾病的证据越来越多，这突出了这种重要性。
