Glasser S W, Korfhagen T R, Weaver T E, Clark J C, Pilot-Matias T, Meuth J, Fox J L, Whitsett J A
University of Cincinnati, College of Medicine, Department of Pediatrics, Ohio 45267-0541.
J Biol Chem. 1988 Jan 5;263(1):9-12.
In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of Mr = 5,000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. We have characterized the amino-terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated an Mr = 22,000 precursor protein, the active hydrophobic peptide being produced by proteolytic processing to Mr = 5,000-6,000. Two classes of cDNAs encoding SPL(pVal) were identified. mRNA of approximately 900 bases was identified on Northern analysis of fetal and adult RNA. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8.
在早产儿透明膜病中，表面活性物质的缺乏会导致肺不张和呼吸窘迫。已从哺乳动物表面活性物质中分离出分子量为5000 - 14000的疏水表面活性蛋白，这些蛋白在动态压缩过程中可提高磷脂的铺展速率和降低表面张力的特性。我们已对牛、犬和人表面活性物质的乙醚/乙醇提取物中的肺蛋白脂质的氨基末端氨基酸序列进行了表征。鉴定出两种不同的肽，分别称为SPL(pVal)和SPL(Phe)。基于SPL(pVal)富含缬氨酸的氨基末端氨基酸序列设计的寡核苷酸探针，被用于分离编码该人类蛋白的cDNA和基因组DNA，该蛋白因其独特的多聚缬氨酸结构域而被称为表面活性蛋白脂质SPL(pVal)。从cDNA的核苷酸序列推导得出了一个含有SPL(pVal)肽的20870道尔顿前体蛋白的一级结构。对人mRNA标记翻译产物的杂交阻断翻译和免疫沉淀显示出一个分子量为22000的前体蛋白，活性疏水肽是通过蛋白水解加工产生的，分子量为5000 - 6000。鉴定出了两类编码SPL(pVal)的cDNA。在对胎儿和成人RNA的Northern分析中鉴定出了约900个碱基的mRNA。人SPL(pVal) mRNA在成人肺中比在胎儿肺中更丰富。SPL(pVal)基因座被定位到8号染色体。
