The kangaroo cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II with low affinity.
The mammalian cation-independent mannose 6-phosphate receptor (CI-MPR) binds mannose 6-phosphate-bearing glycoproteins and insulin-like growth factor (IGF)-II. However, the CI-MPR from the opossum has been reported to bind bovine IGF-II with low affinity (Dahms, N. M., Brzycki-Wessell, M. A., Ramanujam, K. S., and Seetharam, B. (1993) Endocrinology 133, 440-446). This may reflect the use of a heterologous ligand, or it may represent the intrinsic binding affinity of this receptor. To examine the binding of IGF-II to a marsupial CI-MPR in a homologous system, we have previously purified kangaroo IGF-II (Yandell, C. A., Francis, G. L., Wheldrake, J. F., and Upton, Z. (1998) J. Endocrinol. 156, 195-204), and we now report the purification and characterization of the CI-MPR from kangaroo liver. The interaction of the kangaroo CI-MPR with IGF-II has been examined by ligand blotting, radioreceptor assay, and real-time biomolecular interaction analysis. Using both a heterologous and homologous approach, we have demonstrated that the kangaroo CI-MPR has a lower binding affinity for IGF-II than its eutherian (placental mammal) counterparts. Furthermore, real-time biomolecular interaction analysis revealed that the kangaroo CI-MPR has a higher affinity for kangaroo IGF-II than for human IGF-II. The cDNA sequence of the kangaroo CI-MPR indicates that there is considerable divergence in the area corresponding to the IGF-II binding site of the eutherian receptor. Thus, the acquisition of a high-affinity binding site for regulating IGF-II appears to be a recent event specific to the eutherian lineage.
Yandell
C A
CA
Cooperative Research Centre for Tissue Growth and Repair, P. O. Box 10065, Adelaide B.C., South Australia, Australia, 5000. catherine.yandell@imvs.sa.gov.au
Dunbar
A J
AJ
Wheldrake
J F
JF
Upton
Z
Z
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015153:Blotting, Western; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000737:chemistry; D007614:Macropodidae; D008969:Molecular Sequence Data; D017527:Receptor, IGF Type 2 / Q000302:isolation & purification / Q000378:metabolism*
D008024:Ligands; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II