title: Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor.
abstract: The finding that insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) binding to mouse osteoblasts was capable of being downregulated by IGFBP-5 suggested that the 420-kDa membrane protein, which interacted with IGFBP-5, may be a signaling receptor (Andress, D. L. J. Biol. Chem. 270: 28289-28296, 1995). In the current study, a carboxy-terminal IGFBP-5 peptide, IGFBP-5-(201-218), which was found to competitively inhibit 125I-IGFBP-5 binding and to specifically bind to osteoblast monolayers, was used to affinity-purify the 420-kDa membrane protein. Co-incubation of the affinity-purified membrane protein with [32P]ATP resulted in autophosphorylation at serine residues. Serine phosphorylation of the 420-kDa protein was enhanced by intact IGFBP-5, IGFBP-5-(1-169), and IGFBP-5-(201-218). When the IGFBP-5 receptor was incubated with dephosphorylated casein in the presence of [32P]ATP, casein became phosphorylated on serine residues. These data indicate that IGFBP-5 stimulates the phosphorylation of the IGFBP-5 receptor and suggest that serine/threonine kinase activation may be important in mediating some of the IGF-independent effects of IGFBP-5.
authors.affiliation: Medical Service, Veterans Affairs Medical Center, Seattle 98108, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Andress
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D018975:Insulin-Like Growth Factor Binding Protein 5; D008565:Membrane Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface