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Amylin Receptor Phenotypes Derived from Human Calcitonin Receptor/RAMP Coexpression Exhibit Pharmacological Differences Dependent on Receptor Isoform and Host Cell Environment
Receptor activity modifying proteins (RAMPs) constitute a group of three proteins, designated as RAMP1, 2, and 3, which are able to effect functional changes in some members of the G protein-coupled receptor family. Thus, RAMP1 or RAMP3 can modify the calcitonin receptor (CTR) to also function as a...
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| Published in: | The Journal of pharmacology and experimental therapeutics 2000-07, Vol.294 (1), p.61-72 |
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| container_title | The Journal of pharmacology and experimental therapeutics |
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| creator | Tilakaratne, N Christopoulos, G Zumpe, E T Foord, S M Sexton, P M |
| description | Receptor activity modifying proteins (RAMPs) constitute a group of three proteins, designated as RAMP1, 2, and 3, which are
able to effect functional changes in some members of the G protein-coupled receptor family. Thus, RAMP1 or RAMP3 can modify
the calcitonin receptor (CTR) to also function as a high-affinity amylin receptor-like phenotype. To examine the RAMP/CTR
interaction, individual RAMPs were coexpressed with either of the two human CTR (hCTR) isoforms, the insert negative (hCTR I1â ) or the insert positive (hCTR I1+ ), in Chinese hamster ovary (CHO-P) or African monkey kidney (COS-7) cells. CHO-P cells provide an environment conducive to
a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is
imperative for amylin binding. Also, in CHO-P, hCTR I1â induced amylin binding with all three RAMPs, in contrast to COS-7, where only RAMP1 or RAMP3 generate an amylin receptor
phenotype. hCTR I1+ induced high-affinity amylin binding with any RAMP in either cell line. In COS-7 cells, hCTR I1+ /RAMP-generated receptor displayed high- and low-affinity states, in contrast with the single-state binding seen with hCTR I1â /RAMP-generated receptor, whereas in CHO-P cells a two-affinity state receptor phenotype was evident with both hCTR isoforms.
Endogenous RAMP expression is low and similar between cell lines. The results suggest that CTR/RAMP interaction in these cells
is complex with other cellular factors such as the levels of different G proteins and/or receptor/RAMP stoichiometry following
heterologous coexpression contributing to the ultimate receptor phenotype. |
| format | article |
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able to effect functional changes in some members of the G protein-coupled receptor family. Thus, RAMP1 or RAMP3 can modify
the calcitonin receptor (CTR) to also function as a high-affinity amylin receptor-like phenotype. To examine the RAMP/CTR
interaction, individual RAMPs were coexpressed with either of the two human CTR (hCTR) isoforms, the insert negative (hCTR I1â ) or the insert positive (hCTR I1+ ), in Chinese hamster ovary (CHO-P) or African monkey kidney (COS-7) cells. CHO-P cells provide an environment conducive to
a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is
imperative for amylin binding. Also, in CHO-P, hCTR I1â induced amylin binding with all three RAMPs, in contrast to COS-7, where only RAMP1 or RAMP3 generate an amylin receptor
phenotype. hCTR I1+ induced high-affinity amylin binding with any RAMP in either cell line. In COS-7 cells, hCTR I1+ /RAMP-generated receptor displayed high- and low-affinity states, in contrast with the single-state binding seen with hCTR I1â /RAMP-generated receptor, whereas in CHO-P cells a two-affinity state receptor phenotype was evident with both hCTR isoforms.
Endogenous RAMP expression is low and similar between cell lines. The results suggest that CTR/RAMP interaction in these cells
is complex with other cellular factors such as the levels of different G proteins and/or receptor/RAMP stoichiometry following
heterologous coexpression contributing to the ultimate receptor phenotype.</description><identifier>ISSN: 0022-3565</identifier><identifier>EISSN: 1521-0103</identifier><identifier>PMID: 10871296</identifier><language>eng</language><publisher>United States: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Amyloid - metabolism ; Animals ; CHO Cells ; COS Cells ; Cricetinae ; Humans ; Intracellular Signaling Peptides and Proteins ; Islet Amyloid Polypeptide ; Membrane Proteins - physiology ; Phenotype ; Protein Isoforms - physiology ; Receptor Activity-Modifying Protein 1 ; Receptor Activity-Modifying Protein 3 ; Receptor Activity-Modifying Proteins ; Receptors, Calcitonin - physiology ; Receptors, Islet Amyloid Polypeptide ; Receptors, Peptide - physiology ; Transfection</subject><ispartof>The Journal of pharmacology and experimental therapeutics, 2000-07, Vol.294 (1), p.61-72</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10871296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tilakaratne, N</creatorcontrib><creatorcontrib>Christopoulos, G</creatorcontrib><creatorcontrib>Zumpe, E T</creatorcontrib><creatorcontrib>Foord, S M</creatorcontrib><creatorcontrib>Sexton, P M</creatorcontrib><title>Amylin Receptor Phenotypes Derived from Human Calcitonin Receptor/RAMP Coexpression Exhibit Pharmacological Differences Dependent on Receptor Isoform and Host Cell Environment</title><title>The Journal of pharmacology and experimental therapeutics</title><addtitle>J Pharmacol Exp Ther</addtitle><description>Receptor activity modifying proteins (RAMPs) constitute a group of three proteins, designated as RAMP1, 2, and 3, which are
able to effect functional changes in some members of the G protein-coupled receptor family. Thus, RAMP1 or RAMP3 can modify
the calcitonin receptor (CTR) to also function as a high-affinity amylin receptor-like phenotype. To examine the RAMP/CTR
interaction, individual RAMPs were coexpressed with either of the two human CTR (hCTR) isoforms, the insert negative (hCTR I1â ) or the insert positive (hCTR I1+ ), in Chinese hamster ovary (CHO-P) or African monkey kidney (COS-7) cells. CHO-P cells provide an environment conducive to
a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is
imperative for amylin binding. Also, in CHO-P, hCTR I1â induced amylin binding with all three RAMPs, in contrast to COS-7, where only RAMP1 or RAMP3 generate an amylin receptor
phenotype. hCTR I1+ induced high-affinity amylin binding with any RAMP in either cell line. In COS-7 cells, hCTR I1+ /RAMP-generated receptor displayed high- and low-affinity states, in contrast with the single-state binding seen with hCTR I1â /RAMP-generated receptor, whereas in CHO-P cells a two-affinity state receptor phenotype was evident with both hCTR isoforms.
Endogenous RAMP expression is low and similar between cell lines. The results suggest that CTR/RAMP interaction in these cells
is complex with other cellular factors such as the levels of different G proteins and/or receptor/RAMP stoichiometry following
heterologous coexpression contributing to the ultimate receptor phenotype.</description><subject>Amyloid - metabolism</subject><subject>Animals</subject><subject>CHO Cells</subject><subject>COS Cells</subject><subject>Cricetinae</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Islet Amyloid Polypeptide</subject><subject>Membrane Proteins - physiology</subject><subject>Phenotype</subject><subject>Protein Isoforms - physiology</subject><subject>Receptor Activity-Modifying Protein 1</subject><subject>Receptor Activity-Modifying Protein 3</subject><subject>Receptor Activity-Modifying Proteins</subject><subject>Receptors, Calcitonin - physiology</subject><subject>Receptors, Islet Amyloid Polypeptide</subject><subject>Receptors, Peptide - physiology</subject><subject>Transfection</subject><issn>0022-3565</issn><issn>1521-0103</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNpNkE1PhDAQQInR6Lr6F0wveiP2iwLHDa6uicbNRs-kwFRqaIstq_Kr_IsSV6Onubx5M3l70YwklMSYYLYfzTCmNGaJSI6i4xBeMCacC3YYHRGcpYTmYhZ9LszYaYs2UEM_OI_WLVg3jD0EdAVev0GDlHcGrbZGWlTIrtaDs_82LjeL-zUqHHz0HkLQzqLlR6srPUwu6Y2sXeeedS07dKWVAg-2_pb3YBuwA3L_rt8Gp5w3SNoGrVwYUAFdh5b2TXtnzUSfRAdKdgFOf-Y8erpePhar-O7h5rZY3MUtZekQizxlKq9SolKeCMZExXiKM86AY6CKJ1iopsowz2lDcUpETZOMVVVFmczzpmHz6GLn7b173UIYSqNDPT0jLbhtKKd8JKdCTODZD7itDDRl77WRfix_E0_A-Q5o9XP7rj2U_V-WsaQ5L0kpCPsCUdOImA</recordid><startdate>20000701</startdate><enddate>20000701</enddate><creator>Tilakaratne, N</creator><creator>Christopoulos, G</creator><creator>Zumpe, E T</creator><creator>Foord, S M</creator><creator>Sexton, P M</creator><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20000701</creationdate><title>Amylin Receptor Phenotypes Derived from Human Calcitonin Receptor/RAMP Coexpression Exhibit Pharmacological Differences Dependent on Receptor Isoform and Host Cell Environment</title><author>Tilakaratne, N ; Christopoulos, G ; Zumpe, E T ; Foord, S M ; Sexton, P M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h237t-6973f9b71f7456336b3470843e40e2f4506fdb80492d20716c2583bbb23a99dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Amyloid - metabolism</topic><topic>Animals</topic><topic>CHO Cells</topic><topic>COS Cells</topic><topic>Cricetinae</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Islet Amyloid Polypeptide</topic><topic>Membrane Proteins - physiology</topic><topic>Phenotype</topic><topic>Protein Isoforms - physiology</topic><topic>Receptor Activity-Modifying Protein 1</topic><topic>Receptor Activity-Modifying Protein 3</topic><topic>Receptor Activity-Modifying Proteins</topic><topic>Receptors, Calcitonin - physiology</topic><topic>Receptors, Islet Amyloid Polypeptide</topic><topic>Receptors, Peptide - physiology</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tilakaratne, N</creatorcontrib><creatorcontrib>Christopoulos, G</creatorcontrib><creatorcontrib>Zumpe, E T</creatorcontrib><creatorcontrib>Foord, S M</creatorcontrib><creatorcontrib>Sexton, P M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pharmacology and experimental therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tilakaratne, N</au><au>Christopoulos, G</au><au>Zumpe, E T</au><au>Foord, S M</au><au>Sexton, P M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amylin Receptor Phenotypes Derived from Human Calcitonin Receptor/RAMP Coexpression Exhibit Pharmacological Differences Dependent on Receptor Isoform and Host Cell Environment</atitle><jtitle>The Journal of pharmacology and experimental therapeutics</jtitle><addtitle>J Pharmacol Exp Ther</addtitle><date>2000-07-01</date><risdate>2000</risdate><volume>294</volume><issue>1</issue><spage>61</spage><epage>72</epage><pages>61-72</pages><issn>0022-3565</issn><eissn>1521-0103</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Receptor activity modifying proteins (RAMPs) constitute a group of three proteins, designated as RAMP1, 2, and 3, which are
able to effect functional changes in some members of the G protein-coupled receptor family. Thus, RAMP1 or RAMP3 can modify
the calcitonin receptor (CTR) to also function as a high-affinity amylin receptor-like phenotype. To examine the RAMP/CTR
interaction, individual RAMPs were coexpressed with either of the two human CTR (hCTR) isoforms, the insert negative (hCTR I1â ) or the insert positive (hCTR I1+ ), in Chinese hamster ovary (CHO-P) or African monkey kidney (COS-7) cells. CHO-P cells provide an environment conducive to
a low, but significant, level of amylin binding with either hCTR isoform alone, unlike in COS-7, where RAMP coexpression is
imperative for amylin binding. Also, in CHO-P, hCTR I1â induced amylin binding with all three RAMPs, in contrast to COS-7, where only RAMP1 or RAMP3 generate an amylin receptor
phenotype. hCTR I1+ induced high-affinity amylin binding with any RAMP in either cell line. In COS-7 cells, hCTR I1+ /RAMP-generated receptor displayed high- and low-affinity states, in contrast with the single-state binding seen with hCTR I1â /RAMP-generated receptor, whereas in CHO-P cells a two-affinity state receptor phenotype was evident with both hCTR isoforms.
Endogenous RAMP expression is low and similar between cell lines. The results suggest that CTR/RAMP interaction in these cells
is complex with other cellular factors such as the levels of different G proteins and/or receptor/RAMP stoichiometry following
heterologous coexpression contributing to the ultimate receptor phenotype.</abstract><cop>United States</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>10871296</pmid><tpages>12</tpages></addata></record> |
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| ispartof | The Journal of pharmacology and experimental therapeutics, 2000-07, Vol.294 (1), p.61-72 |
| issn | 0022-3565 1521-0103 |
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| source | Medical Journals (Open access) |
| subjects | Amyloid - metabolism Animals CHO Cells COS Cells Cricetinae Humans Intracellular Signaling Peptides and Proteins Islet Amyloid Polypeptide Membrane Proteins - physiology Phenotype Protein Isoforms - physiology Receptor Activity-Modifying Protein 1 Receptor Activity-Modifying Protein 3 Receptor Activity-Modifying Proteins Receptors, Calcitonin - physiology Receptors, Islet Amyloid Polypeptide Receptors, Peptide - physiology Transfection |
| title | Amylin Receptor Phenotypes Derived from Human Calcitonin Receptor/RAMP Coexpression Exhibit Pharmacological Differences Dependent on Receptor Isoform and Host Cell Environment |
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