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      Hybrid and Atypical Insulin/lnsulin-Like Growth Factor I Receptors

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          Abstract

          The insulin receptor and type 1 insulin-like growth factor (IGF) receptor as classically described are each the product of a single gene. Various receptor subtypes have been described, however, with distinct structures or binding properties. Two of these subtypes have been studied, namely hybrid and atypical IGF-I receptors. Hybrid receptors contain aβ halves of both the insulin and the IGF receptor. They are identifiable as a high-affinity IGF-I-binding species reacting with both IGF-receptor-specific and insulin-receptor-specific monoclonal antibodies, and account for a substantial fraction of IGF receptor in many mammalian tissues. Hybrid receptors purified from human placenta bind IGF-I with approximately 25-fold higher affinity than insulin, the affinity for insulin being 10-fold less than that of the classical insulin receptor. It is therefore likely that hybrids will respond more readily to IGF-I than to insulin in vivo. Atypical IGF receptors are characterized by an ability to bind insulin as well as IGFs with relatively high affinity, but are immunologically indistinguishable from classical IGF receptor and do not react with insulin receptor-specific antibodies. The structural basis of atypical binding behaviour is unknown, though the effect is mimicked by binding of certain anti-IGF receptor monoclonal antibodies, which dramatically increase the affinity of the IGF receptor for insulin. Specific physiological roles have not been demonstrated for hybrid or atypical receptors, but the available information concerning their distribution and properties suggests that these receptor subtypes may have an important influence on the specificity of action of insulin and IGFs in vivo.

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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
          : 56-65
          Affiliations
          Department of Clinical Biochemistry, Addenbrooke’s Hospital, University of Cambridge, UK
          Article
          183962 Horm Res 1994;41:56–65
          10.1159/000183962
          8088705
          © 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: 10
          Categories
          Symposium Session I: The Insulin and IGF Receptors: Structure and Function

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