Biophysical and biological properties of naturally occurring high molecular weight insulin-like growth factor II variants

Kenneth J. Valenzano, Ellen Heath-Monnig, Sherida E. Tollefsen, Mats Lake, Peter Lobel

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28 Scopus citations


A soluble form of the insulin-like growth factor II/mannose 6-phosphate receptor (sIGF-II/MPR) is present in fetal bovine serum and carries mature 7.5-kDa insulin-like growth factor II (IGF-II) and at least 12 different high molecular weight (M(r)) IGF-II isoforms (Valenzano, K. J., Remmler, J., and Lobel, P. (1995) J. Biol. Chem. 270, 16441-16448). In this study, we used gel filtration and anion exchange chromatographies to resolve the isoforms into eight fractions that were characterized with respect to their biochemical, biophysical, and biological properties. Each fraction contained one to three major protein species with apparent sizes ranging from 11 to 17 kDa by SDS- polyacrylamide gel electrophoresis. The 11-kDa species contains no post- translational modifications and consists of an extended IGF-II backbone terminating at Gly-87. The remaining high M(r) IGF-II isoforms are also composed of an 87-amino acid IGF-II peptide backbone but contain increasing amounts of sialated, O-linked sugars. Plasmon resonance spectroscopy experiments revealed that all the high M(r) isoforms and mature 7.5-kDa IGF- II bound to immobilized recombinant soluble human IGF-I receptor, recombinant human IGF-binding protein 1, and sIGF-II/MPR with similar kinetics. In addition, radiolabeled tracer experiments demonstrated that both mature and high M(r) IGF-II isoforms have similar binding profiles in fetal bovine serum and have similar affinities for IGF-II-binding proteins secreted from human fibroblasts. Finally, the biological activity of high M(r) IGF-II was shown to be similar to or slightly better than mature IGF-II in stimulating amino acid uptake in fibroblasts and in inducing myoblast differentiation.

Original languageEnglish (US)
Pages (from-to)4804-4813
Number of pages10
JournalJournal of Biological Chemistry
Issue number8
StatePublished - Feb 21 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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