Lin E Y, Orlofsky A, Berger M S, Prystowsky M B
Biology graduate Group, School of Arts and Sciences, University of Pennsylvania, Philadelphia 19104.
J Immunol. 1993 Aug 15;151(4):1979-88.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF-inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）通过诱导特定基因的表达来刺激造血细胞的增殖、分化和功能激活。作为对GM-CSF调控基因表达研究的一部分，我们之前鉴定出了一个新的小鼠GM-CSF诱导基因A1。在本报告中，我们给出了A1 mRNA的完整核苷酸序列以及部分5'侧翼区域，并描述了该基因的表达模式。结果表明，A1是一个造血组织特异性基因，在包括辅助性T淋巴细胞、巨噬细胞和中性粒细胞在内的多种造血细胞谱系中表达。在小鼠骨髓来源的巨噬细胞中，GM-CSF可快速短暂地诱导A1基因表达，且这种诱导不依赖于从头合成蛋白质。除GM-CSF外，在巨噬细胞中，脂多糖（LPS）也可短暂诱导A1 mRNA积累。这种诱导不是由白细胞介素-1α（IL-1α）或白细胞介素-6（IL-6）介导的，这两种细胞因子均不刺激A1。在髓系前体细胞系32D cl3中，粒细胞集落刺激因子刺激髓系细胞分化过程中可稳定诱导A1基因表达。A1信息编码一个预测的多肽，其相对分子质量为20,024，且无信号肽。该肽序列包含一个80个氨基酸的区域，与bcl-2以及最近描述的bcl-2相关基因MCL1具有相似性。这些数据表明，A1是一个新的早期反应基因，其表达与多种刺激相关，且发生在多种造血细胞类型中。
