{
    "title": "The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.",
    "journal": "Proc. Natl. Acad. Sci. U.S.A.",
    "date": "1999",
    "authors": "Sottrup-Jensen L., Yates J.R. III, Gleich G.J., Oxvig C., Overgaard M.T., Lawrence J.B., Conover C.A., Hays L.G.",
    "reference": {
        "type": "PubMed",
        "id": "10077652",
        "url": "https://pubmed.ncbi.nlm.nih.gov/10077652"
    },
    "referenced_proteins": [
        "Q13219-1"
    ],
    "referenced_glycans": [],
    "species": [
        {
            "name": "Homo sapiens",
            "taxid": 9606,
            "evidence": [
                {
                    "database": "UniProtKB",
                    "id": "Q13219",
                    "url": "https://www.uniprot.org/uniprot/Q13219"
                }
            ],
            "common_name": "Human"
        }
    ],
    "record_id": "pubmed.10077652",
    "abstract": "Proteolytic cleavage of the six known insulin-like growth factor binding proteins (IGFBPs) is a powerful means of rapid structure and function modification of these important growth-regulatory proteins. Intact IGFBP-4 is a potent inhibitor of IGF action in vitro, and cleavage of IGFBP-4 has been shown to abolish its ability to inhibit IGF stimulatory effects in a variety of systems, suggesting that IGFBP-4 proteolysis acts as a positive regulator of IGF bioavailability. Here we report the isolation of an IGF-dependent IGFBP-4-specific protease from human fibroblast-conditioned media and its identification by mass spectrometry microsequencing as pregnancy-associated plasma protein-A (PAPP-A), a protein of unknown function found in high concentrations in the maternal circulation during pregnancy. Antibodies raised against PAPP-A both inhibited and immunodepleted IGFBP-4 protease activity in human fibroblast-conditioned media. Moreover, PAPP-A purified from pregnancy sera had IGF-dependent IGFBP-4 protease activity. PAPP-A mRNA was expressed by the human fibroblasts and osteoblasts, and PAPP-A protein was secreted into the culture medium. In conclusion, we have identified an IGF-dependent IGFBP protease and at the same time assigned a function to PAPP-A. This represents an unanticipated union of two areas of research that were not linked in any way before this report.",
    "glycosylation": [],
    "mutagenesis": [],
    "snv": [],
    "phosphorylation": [],
    "glycation": []
}