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The bovine mannose 6-phosphate/insulin-like growth factor II receptor. Localization of the insulin-like growth factor II binding site to domains 5-11. J Biol Chem 1994 Feb 04;269(5):3802-9

Date

02/04/1994

Pubmed ID

8106425

Scopus ID

2-s2.0-0028101930 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) binds two distinct ligands, mannose 6-phosphate (Man-6-P) and insulin-like growth factor II (IGF-II). The extracytoplasmic region of the receptor is composed of 15 homologous repeating domains and domains 1-3 and 7-9 have been shown to contain the two Man-6-P binding sites. To determine the location of the single IGF-II binding site, truncated forms of the M6P/IGF-II receptor were expressed transiently in COS-1 cells and assayed for their ability to bind iodinated human recombinant IGF-II. The binding of [125I]IGF-II to the receptors in the presence or absence of excess unlabeled IGF-II, IGF-I, or insulin was determined by incubation with homobifunctional cross-linking agents followed by SDS-polyacrylamide gel electrophoresis. These binding studies demonstrated that a construct encoding domains 5-11 bound 0.9 mol of IGF-II/mol of receptor, whereas a construct encoding domains 5-10 exhibited no detectable binding to IGF-II. These results indicate that the IGF-II binding site of the M6P/IGF-II receptor is contained within domains 5-11 and that residues in domain 11 play an important role in IGF-II binding.

Author List

Dahms NM, Wick DA, Brzycki-Wessell MA

Author

Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Binding Sites
Cattle
Chromatography, Affinity
Electrophoresis, Polyacrylamide Gel
Humans
Insulin
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Mannosephosphates
Molecular Sequence Data
Molecular Weight
Mutagenesis, Site-Directed
Oligodeoxyribonucleotides
Receptor, IGF Type 2
Recombinant Proteins
Restriction Mapping
Sequence Deletion