Palfree R G, Sadro L C, Solomon S
Department of Biochemistry, McGill University Montreal, Quebec, Canada.
Mol Endocrinol. 1993 Feb;7(2):199-205. doi: 10.1210/mend.7.2.8469233.
The human neutrophil-derived cationic peptide HP-4 exhibits corticostatic activity on adrenal cells and is an L-type calcium channel agonist at nanomolar concentrations. Complementary DNA clones encoding the HP-4 precursor have been isolated from a human bone marrow cDNA library by screening with oligonucleotide probes. The nucleotide sequence shares about 72% identity with the cDNA encoding defensin HP-1, but differs from it, and from other genes of this family characterized to date, by an extra 83-base segment. This extra segment is not adjacent to an intron and is apparently the result of a recent duplication within the coding region corresponding to most of the mature HP-4 peptide. The predicted amino acid sequence shows the HP-4 precursor structure to be typical of this family of molecules. By analysis of DNA from a pannel of hamster/human hybrid cell lines, the HP-4 gene was found to be on chromosome 8, as is the gene for human peptide HP-1. Comparison with the few sequences of other corticostatin/defensin genes available does not indicate distinct lineages of corticostatic and noncorticostatic peptides, since HP-1 and HP-4 cDNA sequences share more identity with each other than either shares with cDNAs encoding rabbit MCP-1 or MCP-2, or guinea pig GNCP-1.
人中性粒细胞衍生的阳离子肽HP-4对肾上腺细胞具有皮质抑制活性,在纳摩尔浓度下是一种L型钙通道激动剂。通过用寡核苷酸探针筛选,已从人骨髓cDNA文库中分离出编码HP-4前体的互补DNA克隆。该核苷酸序列与编码防御素HP-1的cDNA具有约72%的同一性,但与之不同,并且与该家族迄今已鉴定的其他基因不同之处在于有一个额外的83个碱基的片段。这个额外的片段不与内含子相邻,显然是对应于大部分成熟HP-4肽的编码区域内最近一次复制的结果。预测的氨基酸序列显示HP-4前体结构是该分子家族的典型结构。通过对一组仓鼠/人杂交细胞系的DNA分析,发现HP-4基因位于8号染色体上,人肽HP-1的基因也位于8号染色体上。与现有的其他皮质抑制素/防御素基因的少数序列进行比较,并未表明皮质抑制肽和非皮质抑制肽有明显的谱系,因为HP-1和HP-4的cDNA序列彼此之间的同一性比它们与编码兔MCP-1或MCP-2或豚鼠GNCP-1的cDNA的同一性更高。