title: Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.
abstract: Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.
authors.affiliation: Institute of Biochemistry II, University of Göttingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Braulke
authors.forename: M
authors.initials: M
authors.lastname: Claussen
authors.forename: P
authors.initials: P
authors.lastname: Saftig
authors.forename: M
authors.initials: M
authors.lastname: Wendland
authors.forename: K
authors.initials: K
authors.lastname: Neifer
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: J
authors.initials: J
authors.lastname: Zapf
authors.forename: K
authors.initials: K
authors.lastname: von Figura
authors.forename: C
authors.initials: C
authors.lastname: Peters
mesh_terms: D000818:Animals; D002402:Cathepsin D / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D051379:Mice
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D002402:Cathepsin D