title: Mannose 6-phosphate/insulin-like growth factor II receptor in I-cell disease fibroblasts: increased synthesis and defective regulation of cell surface expression.
abstract: The amount of mannose 6-phosphate/IGF II receptors in fibroblasts from five I-cell patients was about 2-fold higher than in control fibroblasts. The elevated receptor concentration, which led to a higher binding and uptake of mannose 6-phosphate containing ligands and to a higher binding of IGF II resulted from an increased rate of synthesis, while the stability of the receptor was comparable to that in control fibroblasts. Control fibroblasts respond to mannose 6-phosphate, IGF I, IGF II and tumor promoting phorbol esters with a rapid redistribution of mannose 6-phosphate/IGF II receptors from internal membranes to the cell surface. In I-cell fibroblasts only a moderate increase in cell surface receptors was seen after exposure to these effectors. In contrast to control fibroblasts the treatment of I-cell fibroblasts with lysosomotropic amines failed to affect the mannose 6-phosphate containing ligand binding to the receptor. These data provide evidence for multiple potential regulatory sites in intracellular mannose 6-phosphate/IGF II receptor pathway which differ in control and I-cell fibroblasts.
authors.affiliation: Georg-August-Universität, Abt. Biochemie II, Göttingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Braulke
authors.forename: S
authors.initials: S
authors.lastname: Tippmer
authors.forename: U
authors.initials: U
authors.lastname: Matzner
authors.forename: C
authors.initials: C
authors.lastname: Gartung
authors.forename: K
authors.initials: K
authors.lastname: von Figura
mesh_terms: D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002738:Chloroquine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D009081:Mucolipidoses / Q000235:genetics / Q000378:metabolism*; D010703:Phorbol Esters / Q000378:metabolism; D011869:Radioligand Assay; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism
chemical_list: D008360:Mannosephosphates; D010703:Phorbol Esters; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D013002:Somatomedins; C027693:mannose-6-phosphate; D002738:Chloroquine