Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors
We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of hormone-receptor interactions in the insulin and insul...
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| Veröffentlicht in: | The Journal of biological chemistry 1993-02, Vol.268 (5), p.3044-3047 |
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| container_title | The Journal of biological chemistry |
| container_volume | 268 |
| creator | SCHÄFFER, L KJELDSEN, T ANDERSEN, A. S WIBERG, F. C LARSEN, U. D CARA, J. F MIRMIRA, R. G NAKAGAWA, S. H TAGER, H. S |
| description | We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like
growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of
hormone-receptor interactions in the insulin and insulin-like growth factor-I systems. Our findings, obtained through the
study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show
that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of
appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the
affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like
growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor
receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related
hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities
and selectivities. |
| doi_str_mv | 10.1016/S0021-9258(18)53656-5 |
| format | Article |
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growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of
hormone-receptor interactions in the insulin and insulin-like growth factor-I systems. Our findings, obtained through the
study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show
that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of
appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the
affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like
growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor
receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related
hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities
and selectivities.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(18)53656-5</identifier><identifier>PMID: 8428981</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>binding ; Binding Sites ; Biological and medical sciences ; Cell receptors ; Cell structures and functions ; chimeras ; Fundamental and applied biological sciences. Psychology ; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors ; Humans ; hybrids ; insulin ; Insulin - genetics ; Insulin - metabolism ; insulin-like growth factor I ; Insulin-Like Growth Factor I - genetics ; Insulin-Like Growth Factor I - metabolism ; interaction ; Kinetics ; Ligands ; Models, Structural ; Molecular and cellular biology ; Protein Multimerization ; Receptor, IGF Type 1 - genetics ; Receptor, IGF Type 1 - metabolism ; receptors ; Recombinant Fusion Proteins - metabolism ; Sequence Deletion ; specificity</subject><ispartof>The Journal of biological chemistry, 1993-02, Vol.268 (5), p.3044-3047</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-fb0afb874a2f94dd7080769be086b4f4dbe036b07dfbe13e88dc83fa62bc81ea3</citedby><cites>FETCH-LOGICAL-c438t-fb0afb874a2f94dd7080769be086b4f4dbe036b07dfbe13e88dc83fa62bc81ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3888814$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8428981$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHÄFFER, L</creatorcontrib><creatorcontrib>KJELDSEN, T</creatorcontrib><creatorcontrib>ANDERSEN, A. S</creatorcontrib><creatorcontrib>WIBERG, F. C</creatorcontrib><creatorcontrib>LARSEN, U. D</creatorcontrib><creatorcontrib>CARA, J. F</creatorcontrib><creatorcontrib>MIRMIRA, R. G</creatorcontrib><creatorcontrib>NAKAGAWA, S. H</creatorcontrib><creatorcontrib>TAGER, H. S</creatorcontrib><title>Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like
growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of
hormone-receptor interactions in the insulin and insulin-like growth factor-I systems. Our findings, obtained through the
study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show
that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of
appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the
affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like
growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor
receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related
hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities
and selectivities.</description><subject>binding</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>chimeras</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</subject><subject>Humans</subject><subject>hybrids</subject><subject>insulin</subject><subject>Insulin - genetics</subject><subject>Insulin - metabolism</subject><subject>insulin-like growth factor I</subject><subject>Insulin-Like Growth Factor I - genetics</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>interaction</subject><subject>Kinetics</subject><subject>Ligands</subject><subject>Models, Structural</subject><subject>Molecular and cellular biology</subject><subject>Protein Multimerization</subject><subject>Receptor, IGF Type 1 - genetics</subject><subject>Receptor, IGF Type 1 - metabolism</subject><subject>receptors</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Sequence Deletion</subject><subject>specificity</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1rHDEMhk1pSLfb_oSAKaW0h2nsscejOYbQj4VAD2mhN2N75B2387G1Z1n2D_R3x8kOe4sOkpCeV4KXkCvOPnPG1fU9YyUvmrKCjxw-VUJVqqhekBVnIApR8d8vyeqMvCKvU_rDcsiGX5JLkCU0wFfk_2acMRo3h2lMdPLU0O5oY2hpGNO-D-P1Uos-_EW6jdNh7qjPgikWG2pG009begh56LowYAzurJyPO6Qb-vwBGtHhLjfpDbnwpk_4dqlr8uvrl5-334u7H982tzd3hZMC5sJbZryFWprSN7JtawasVo1FBspKL9vcCWVZ3XqLXCBA60B4o0rrgKMRa_LhdHcXp397TLMeQnLY92bEaZ80V7KsQUEGqxPo4pRSRK93MQwmHjVn-tF__eS_fjRXc9BP_ue8JlfLg70dsD2rFsPz_v2yN8mZ3kczupDOmIAcXGbs3QnrwrY7hIjahsl1OOhS5WdaMCnFA_9onOg</recordid><startdate>19930215</startdate><enddate>19930215</enddate><creator>SCHÄFFER, L</creator><creator>KJELDSEN, T</creator><creator>ANDERSEN, A. S</creator><creator>WIBERG, F. C</creator><creator>LARSEN, U. D</creator><creator>CARA, J. F</creator><creator>MIRMIRA, R. G</creator><creator>NAKAGAWA, S. H</creator><creator>TAGER, H. S</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope></search><sort><creationdate>19930215</creationdate><title>Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors</title><author>SCHÄFFER, L ; KJELDSEN, T ; ANDERSEN, A. S ; WIBERG, F. C ; LARSEN, U. D ; CARA, J. F ; MIRMIRA, R. G ; NAKAGAWA, S. H ; TAGER, H. S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-fb0afb874a2f94dd7080769be086b4f4dbe036b07dfbe13e88dc83fa62bc81ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>binding</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cell receptors</topic><topic>Cell structures and functions</topic><topic>chimeras</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</topic><topic>Humans</topic><topic>hybrids</topic><topic>insulin</topic><topic>Insulin - genetics</topic><topic>Insulin - metabolism</topic><topic>insulin-like growth factor I</topic><topic>Insulin-Like Growth Factor I - genetics</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>interaction</topic><topic>Kinetics</topic><topic>Ligands</topic><topic>Models, Structural</topic><topic>Molecular and cellular biology</topic><topic>Protein Multimerization</topic><topic>Receptor, IGF Type 1 - genetics</topic><topic>Receptor, IGF Type 1 - metabolism</topic><topic>receptors</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Sequence Deletion</topic><topic>specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHÄFFER, L</creatorcontrib><creatorcontrib>KJELDSEN, T</creatorcontrib><creatorcontrib>ANDERSEN, A. S</creatorcontrib><creatorcontrib>WIBERG, F. C</creatorcontrib><creatorcontrib>LARSEN, U. D</creatorcontrib><creatorcontrib>CARA, J. F</creatorcontrib><creatorcontrib>MIRMIRA, R. G</creatorcontrib><creatorcontrib>NAKAGAWA, S. H</creatorcontrib><creatorcontrib>TAGER, H. S</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHÄFFER, L</au><au>KJELDSEN, T</au><au>ANDERSEN, A. S</au><au>WIBERG, F. C</au><au>LARSEN, U. D</au><au>CARA, J. F</au><au>MIRMIRA, R. G</au><au>NAKAGAWA, S. H</au><au>TAGER, H. S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1993-02-15</date><risdate>1993</risdate><volume>268</volume><issue>5</issue><spage>3044</spage><epage>3047</epage><pages>3044-3047</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like
growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of
hormone-receptor interactions in the insulin and insulin-like growth factor-I systems. Our findings, obtained through the
study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show
that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of
appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the
affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like
growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor
receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related
hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities
and selectivities.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8428981</pmid><doi>10.1016/S0021-9258(18)53656-5</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 1993-02, Vol.268 (5), p.3044-3047 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16427868 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | binding Binding Sites Biological and medical sciences Cell receptors Cell structures and functions chimeras Fundamental and applied biological sciences. Psychology Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors Humans hybrids insulin Insulin - genetics Insulin - metabolism insulin-like growth factor I Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - metabolism interaction Kinetics Ligands Models, Structural Molecular and cellular biology Protein Multimerization Receptor, IGF Type 1 - genetics Receptor, IGF Type 1 - metabolism receptors Recombinant Fusion Proteins - metabolism Sequence Deletion specificity |
| title | Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors |
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