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      Analysis of the Interaction of Insulin-Like Growth Factor I (IGF-I) Analogs with the IGF-I Receptor and IGF-Binding Proteins

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          Abstract

          Analogs of insulin-like growth factor I (IGF-I) have been prepared by site-directed mutagenesis in order to determine the structural domains of IGF-I required for IGF receptor and IGF-binding protein (IGFBP) binding, and to produce analogs with selective affinity for receptors or IGFBP to determine the physiologic roles of these proteins. Distinct domains of IGF-I are important for maintaining high affinity for the IGF-I receptor and for the various species of IGFBPs. The analogs that selectively bind to the receptor and have reduced affinity for IGFBPs have proved useful in determining the relative importance of IGFBPs in the regulation of the biologic activity of IGF-I. In most cases, analogs with reduced affinity for IGFBP have increased or normal potency compared with IGF-I. These data suggest that binding of IGF-I to IGFBP inhibits its biologic activity. As these analogs are cleared more rapidly after parenteral administration, however, they do not provide a significant advantage over IGF-I for in vivo administration. Analogs with poor affinity for the receptor have also been useful in demonstrating that a given activity of IGF-I is mediated by the type 1 IGF receptor. These studies confirm that the role of these various proteins in IGF-I action is complex, and may be cell specific or tissue-type specific.

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          Author and article information

          Journal
          HRE
          Horm Res Paediatr
          10.1159/issn.1663-2818
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-6003-0
          978-3-318-00608-7
          1663-2818
          1663-2826
          1994
          1994
          05 December 2008
          : 41
          : Suppl 2
          : 80-86
          Affiliations
          Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, N.J., USA
          Article
          183965 Horm Res 1994;41:80–86
          10.1159/000183965
          7522208
          © 1994 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 7
          Categories
          Symposium Session I: The Insulin and IGF Receptors: Structure and Function

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