ISOLATION AND SEQUENCE OF THE GRANULIN PRECURSOR CDNA FROM HUMAN BONE-MARROW REVEALS TANDEM CYSTEINE-RICH GRANULIN DOMAINS

Granulins are candidate growth factors recently discovered in human and rat inflammatory leukocytes and bone marrow. Two granulin homologs, epithelin 1 and 2, occur in the rat kidney. Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro. Here we show by cDNA analysis that the prepropeptide for the human granulins is a 593-residue glycoprotein, containing seven tandem repeats of the 12-cysteine granulin domain. By Northern blot analysis, gene expression was seen in myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts and was seen very strongly in epithelial cell lines. Some epithelial cell lines respond to the mature peptide and express the gene. Among tissues examined, the kidney had the highest levels of granulin mRNA.