HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valenzano, K. J. Articles by Lobel, P. Search for Related Content PubMed PubMed Citation Articles by Valenzano, K. J. Articles by Lobel, P. Social Bookmarking                      What's this?

Volume 272, Number 8, Issue of February 21, 1997 pp. 4804-4813
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Biophysical and Biological Properties of Naturally Occurring High Molecular Weight Insulin-like Growth Factor II Variants

(Received for publication, September 24, 1996, and in revised form, November 11, 1996)

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

From the  Center for Advanced Biotechnology and Medicine and Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, the ^¶ Department of Pediatrics, Washington University School of Medicine, and Division of Endocrinology and Metabolism, St. Louis Children's Hospital, St. Louis, Missouri 63110, and  Pharmacia Upjohn AB, Biopharmaceuticals R & D, Strandbergsgatan 49, S-112 87 Stockholm, Sweden

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Qiu, J.-Y. Jiang, M. Bell, B. K. Tsang, and A. Gruslin Activation of Endoproteolytic Processing of Insulin-Like Growth Factor-II in Fetal, Early Postnatal, and Pregnant Rats and Persistence of Circulating Levels in Postnatal Life Endocrinology, October 1, 2007; 148(10): 4803 - 4811. [Abstract] [Full Text] [PDF]

				J. Cornish, K. E. Callon, U. Bava, M. Watson, X. Xu, J. M. Lin, V. A. Chan, A. B. Grey, D. Naot, C. M. Buchanan, et al. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E117 - E122. [Abstract] [Full Text] [PDF]

				Q. Qiu, A. Basak, M. Mbikay, B. K. Tsang, and A. Gruslin Role of pro-IGF-II processing by proprotein convertase 4 in human placental development PNAS, August 2, 2005; 102(31): 11047 - 11052. [Abstract] [Full Text] [PDF]

				J. van Doorn, C. M. Hoogerbrugge, J. G. Koster, R. J. Bloemen, K. Hoekman, A. H. Mudde, and S. C. van Buul-Offers Antibodies Directed against the E Region of Pro-Insulin-like Growth Factor-II Used to Evaluate Non-Islet Cell Tumor-induced Hypoglycemia Clin. Chem., October 1, 2002; 48(10): 1739 - 1750. [Abstract] [Full Text] [PDF]

				S. J. Duguay, Y. Jin, J. Stein, A. N. Duguay, P. Gardner, and D. F. Steiner Post-translational Processing of the Insulin-like Growth Factor-2 Precursor. ANALYSIS OF O-GLYCOSYLATION AND ENDOPROTEOLYSIS J. Biol. Chem., July 17, 1998; 273(29): 18443 - 18451. [Abstract] [Full Text] [PDF]

				J. Linnell, G. Groeger, and A. B. Hassan Real Time Kinetics of Insulin-like Growth Factor II (IGF-II) Interaction with the IGF-II/Mannose 6-Phosphate Receptor. THE EFFECTS OF DOMAIN 13 AND pH J. Biol. Chem., June 22, 2001; 276(26): 23986 - 23991. [Abstract] [Full Text] [PDF]