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Article: Identification of two novel chicken GHRH receptor splice variants: Implications for the roles of aspartate 56 in the receptor activation and direct ligand-receptor interaction

TitleIdentification of two novel chicken GHRH receptor splice variants: Implications for the roles of aspartate 56 in the receptor activation and direct ligand-receptor interaction
Authors
Issue Date2007
PublisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org
Citation
Journal Of Endocrinology, 2007, v. 195 n. 3, p. 525-536 How to Cite?
AbstractIn this study, two novel GHRHR receptor splice variants, named chicken GHRHR-v1 (cGHRHR-v1) and cGHRHR-v2 respectively, were identified from chicken pituitary using RT-PCR assay. cGHR-HR-v1 is characterized by an N-terminal deletion of 36 amino acid residues, including an aspartate at position 56 (Asp56) conserved in G protein-coupled receptor B-I subfamily. cGHRHR-v2 is a carboxyl-terminal truncated receptor variant with four putative transmembrane domains, which arose from alternative use of a splice acceptor site on intron 8. Using the pGL3-CRE-luciferase reporter system, the functionality of the two variants was examined in Chinese hamster ovary cells. cGHRHR-v1 was shown to be capable of transmitting signal upon agonist stimulation, but cGHRHR-v2 could not. Both GHRH and pituitary adenylate cyclase-activating peptide (PACAP) could activate cGHRHR-v1 at high dosages (GHRH ≥10-8 M; PACAP ≥10-6 M) and GHRH was much more potent than PACAP, suggesting that cGHRHR-v1 is a functional membrane-spanning receptor with an impairment in high-affinity ligand binding, rather than in receptor activation and ligand-binding specificity. This finding also points out the possibility that Asp56 is not a critical determinant for receptor activation and direct ligand-receptor interaction. To substantiate this hypothesis, using site-directed mutagenesis, two receptor mutants with replacement of Asp56 by Ala or Gly were generated. Expectedly, chicken or human GHRH could still activate both receptor mutants with reduced potencies (about 2- to 14-fold less potent). Taken together, our findings not only suggest that cGHRHR variants may play a role in controlling normal pituitary functions, but also support that Asp56 is nonessential for receptor activation and direct ligand-receptor interaction. © 2007 Society for Endocrinology.
Persistent Identifierhttp://hdl.handle.net/10722/89241
ISSN
2015 Impact Factor: 4.498
2015 SCImago Journal Rankings: 1.910
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, CYen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorKwok, AHYen_HK
dc.contributor.authorLeung, FCen_HK
dc.date.accessioned2010-09-06T09:54:20Z-
dc.date.available2010-09-06T09:54:20Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Endocrinology, 2007, v. 195 n. 3, p. 525-536en_HK
dc.identifier.issn0022-0795en_HK
dc.identifier.urihttp://hdl.handle.net/10722/89241-
dc.description.abstractIn this study, two novel GHRHR receptor splice variants, named chicken GHRHR-v1 (cGHRHR-v1) and cGHRHR-v2 respectively, were identified from chicken pituitary using RT-PCR assay. cGHR-HR-v1 is characterized by an N-terminal deletion of 36 amino acid residues, including an aspartate at position 56 (Asp56) conserved in G protein-coupled receptor B-I subfamily. cGHRHR-v2 is a carboxyl-terminal truncated receptor variant with four putative transmembrane domains, which arose from alternative use of a splice acceptor site on intron 8. Using the pGL3-CRE-luciferase reporter system, the functionality of the two variants was examined in Chinese hamster ovary cells. cGHRHR-v1 was shown to be capable of transmitting signal upon agonist stimulation, but cGHRHR-v2 could not. Both GHRH and pituitary adenylate cyclase-activating peptide (PACAP) could activate cGHRHR-v1 at high dosages (GHRH ≥10-8 M; PACAP ≥10-6 M) and GHRH was much more potent than PACAP, suggesting that cGHRHR-v1 is a functional membrane-spanning receptor with an impairment in high-affinity ligand binding, rather than in receptor activation and ligand-binding specificity. This finding also points out the possibility that Asp56 is not a critical determinant for receptor activation and direct ligand-receptor interaction. To substantiate this hypothesis, using site-directed mutagenesis, two receptor mutants with replacement of Asp56 by Ala or Gly were generated. Expectedly, chicken or human GHRH could still activate both receptor mutants with reduced potencies (about 2- to 14-fold less potent). Taken together, our findings not only suggest that cGHRHR variants may play a role in controlling normal pituitary functions, but also support that Asp56 is nonessential for receptor activation and direct ligand-receptor interaction. © 2007 Society for Endocrinology.en_HK
dc.languageengen_HK
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.orgen_HK
dc.relation.ispartofJournal of Endocrinologyen_HK
dc.rightsJournal of Endocrinology. Copyright © Society for Endocrinology.en_HK
dc.titleIdentification of two novel chicken GHRH receptor splice variants: Implications for the roles of aspartate 56 in the receptor activation and direct ligand-receptor interactionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-0795&volume=195&spage=525&epage=536?&date=2007&atitle=Identification+of+two+novel+chicken+GHRH+receptor+splice+variants:+implications+for+the+roles+of+aspartate+56+in+the+receptor+activation+and+direct+ligand–receptor+interactionen_HK
dc.identifier.emailWang, Y: cdwyj@yahoo.comen_HK
dc.identifier.emailLeung, FC: fcleung@hkucc.hku.hken_HK
dc.identifier.authorityWang, Y=rp00801en_HK
dc.identifier.authorityLeung, FC=rp00731en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1677/JOE-07-0167en_HK
dc.identifier.pmid18000314-
dc.identifier.scopuseid_2-s2.0-38349038168en_HK
dc.identifier.hkuros146217en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-38349038168&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume195en_HK
dc.identifier.issue3en_HK
dc.identifier.spage525en_HK
dc.identifier.epage536en_HK
dc.identifier.isiWOS:000252093700016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWang, CY=16065173000en_HK
dc.identifier.scopusauthoridWang, Y=36062525200en_HK
dc.identifier.scopusauthoridKwok, AHY=27168105100en_HK
dc.identifier.scopusauthoridLeung, FC=7103078633en_HK

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