The cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II

• Published in: The Journal of biological chemistry 1988-02, Vol.263 (6), p.2585-2588
• Main Authors: Tong, P Y, Tollefsen, S E, Kornfeld, S
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carrier Proteins - metabolism; Cations - metabolism; Cattle; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; IGF-II; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - metabolism; Kinetics; liver; mannose 6-phosphate; Mannosephosphates - metabolism; Molecular and cellular biology; Receptor, IGF Type 2; Somatomedins - metabolism; testes
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)69105-7

The bovine cation-independent mannose 6-phosphate receptor (CI-MPR) and the human insulin-like growth factor II (IGF-II) receptor have recently been shown to be 80% identical in their amino acid sequences as deduced from cDNA clones (Morgan, D. O., Edman, J. C., Standring, D. N., Fried, V. A., Smith, M. C., Roth, R. A., and Rutter, W. J. (1987) Nature 329, 301-307). We have studied the binding of IGF-II to affinity-purified CI-MPR in order to obtain direct evidence that the same protein binds mannose 6-phosphate-containing ligands and IGF-II. In equilibrium binding studies, the CI-MPR bound 0.95 mol of IGF-II/mol of receptor with a Kd of 0.2 nM. The pH optimum of binding was 7.4. The addition of mannose 6-phosphate did not affect binding, indicating that the two ligands interact with different binding sites on the receptor. IGF-I bound to the receptor with a much lower affinity (Kd of 0.4 microM), and insulin binding could not be detected. IGF-II did not bind to the cation-dependent mannose 6-phosphate receptor. We conclude that the cation-independent mannose 6-phosphate receptor and the IGF-II receptor are the same protein.