CDNA CLONING OF A HUMAN MESSENGER-RNA PREFERENTIALLY EXPRESSED IN HEMATOPOIETIC-CELLS AND WITH HOMOLOGY TO A GDP-DISSOCIATION INHIBITOR FOR THE RHO-GTP-BINDING PROTEINS

CDNA CLONING OF A HUMAN MESSENGER-RNA PREFERENTIALLY EXPRESSED IN HEMATOPOIETIC-CELLS AND WITH HOMOLOGY TO A GDP-DISSOCIATION INHIBITOR FOR THE RHO-GTP-BINDING PROTEINS
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DOI:
10.1073/pnas.90.4.1479
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发表时间:
1993-02-15
影响因子:
11.1
通讯作者:
LIM, B
LIM, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LELIAS, JM;ADRA, CN;LIM, B

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我们已经鉴定了一种人基因的mRNA,表示为D4,它在造血细胞系和淋巴和骨髓来源的正常细胞中以非常高的水平表达。在非造血组织中,1.5 kb的转录物不存在或仅在低水平下可检测到。D4编码与rhoGDI同源的201个氨基酸的蛋白质,rhoGDI是ras同源蛋白rho的GDP解离的抑制剂。D4还可能作为小GTP结合蛋白的鸟嘌呤核苷酸交换的调节剂发挥作用。相似大小的同源转录物也优先在鼠造血组织中表达。当全能小鼠胚胎干细胞在体外发育成造血细胞时,该基因随着造血的开始而被激活。当造血细胞系被诱导分化时,D4的表达被调节。因此,D4似乎是一个发育调控基因。D4在造血细胞中的优先表达表明其可能在造血细胞的生长和分化过程中起重要作用。越来越多的证据表明G蛋白的调节因子参与临床疾病,这一重要性得到了强调。
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.