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- Publisher Website: 10.1016/j.febslet.2004.08.088
- Scopus: eid_2-s2.0-7544230057
- PMID: 15527776
- WOS: WOS:000225128600025
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Article: Signal transduction mechanism of the seabream growth hormone secretagogue receptor
Title | Signal transduction mechanism of the seabream growth hormone secretagogue receptor |
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Authors | |
Keywords | Acanthopagrus schlegeli Black seabream Functional expression in cultured eukaryotic cell Growth hormone secretagogue receptor Signal transduction |
Issue Date | 2004 |
Citation | FEBS Letters, 2004, v. 577, n. 1-2, p. 147-153 How to Cite? |
Abstract | We have recently cloned the full-length cDNAs of the two growth hormone secretagogue receptor (GHSR) subtypes from a teleost species, the black seabream (Acanthopagrus schlegeli) [Mol. Cell. Endocrinol. 214 (2004) 81], namely sbGHSR-1a and sbGHSR-1b. Functional expression of these two receptor constructs in human embryonic kidney 293 (HEK293) cells indicated that stimulation of sbGHSR-1a by growth hormone secretagogues (GHS) could evoke increases in intracellular Ca2+ concentration ([Ca2+]i), whereas sbGHSR-1b appeared to play an inhibitory role on the signal transduction activity of sbGHSR-1a. In the present study, we have further investigated the signal transduction mechanism of sbGHSR-1a. The peptide GHS GHRP-6 and the non-peptide GHS L163,540 were able to trigger a receptor specific and phospholipase C (PLC)-dependent elevation of [Ca2+]i in HEK293 cells stably expressing sbGHSR-1a. This GHS-induced calcium mobilization was also dependent on protein kinase C activated L-type calcium channel opening. It was found that sbGHSR-1a could function in an agonist-independent manner as it exhibited a high basal activity of inositol phosphate production in the absence of GHS, indicating that the fish receptor is constitutively active. In addition, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) were found to be activated upon stimulation of sbGHSR-1a by GHRP-6. This observation provides direct evidence in the coupling of sbGHSR-1a to ERK1/2 activation. Neither Gs nor Gi proteins are coupled to the receptor, as GHS did not induce cAMP production nor inhibit forskolin-stimulated cAMP accumulation in the sbGHSR-1a bearing cells. Furthermore, the ability of the GHSR antagonist D-Lys(3)-GHRP-6 to inhibit basal PLC and basal ERK1/2 activity suggests that this compound is an inverse agonist. In summary, the sbGHSR-1a appears to couple through the Gq/11-mediated pathway to activate PLC, resulting in increased IP3 production and Ca2+ mobilization from both intracellular and extracellular stores. Moreover, sbGHSR-1a may trigger multiple signal transduction cascades to exert its physiological functions. © 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
Persistent Identifier | http://hdl.handle.net/10722/225079 |
ISSN | 2023 Impact Factor: 3.0 2023 SCImago Journal Rankings: 1.208 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chan, Chi Bun | - |
dc.contributor.author | Leung, Po Ki | - |
dc.contributor.author | Wise, Helen | - |
dc.contributor.author | Cheng, Christopher H K | - |
dc.date.accessioned | 2016-04-18T11:16:43Z | - |
dc.date.available | 2016-04-18T11:16:43Z | - |
dc.date.issued | 2004 | - |
dc.identifier.citation | FEBS Letters, 2004, v. 577, n. 1-2, p. 147-153 | - |
dc.identifier.issn | 0014-5793 | - |
dc.identifier.uri | http://hdl.handle.net/10722/225079 | - |
dc.description.abstract | We have recently cloned the full-length cDNAs of the two growth hormone secretagogue receptor (GHSR) subtypes from a teleost species, the black seabream (Acanthopagrus schlegeli) [Mol. Cell. Endocrinol. 214 (2004) 81], namely sbGHSR-1a and sbGHSR-1b. Functional expression of these two receptor constructs in human embryonic kidney 293 (HEK293) cells indicated that stimulation of sbGHSR-1a by growth hormone secretagogues (GHS) could evoke increases in intracellular Ca2+ concentration ([Ca2+]i), whereas sbGHSR-1b appeared to play an inhibitory role on the signal transduction activity of sbGHSR-1a. In the present study, we have further investigated the signal transduction mechanism of sbGHSR-1a. The peptide GHS GHRP-6 and the non-peptide GHS L163,540 were able to trigger a receptor specific and phospholipase C (PLC)-dependent elevation of [Ca2+]i in HEK293 cells stably expressing sbGHSR-1a. This GHS-induced calcium mobilization was also dependent on protein kinase C activated L-type calcium channel opening. It was found that sbGHSR-1a could function in an agonist-independent manner as it exhibited a high basal activity of inositol phosphate production in the absence of GHS, indicating that the fish receptor is constitutively active. In addition, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) were found to be activated upon stimulation of sbGHSR-1a by GHRP-6. This observation provides direct evidence in the coupling of sbGHSR-1a to ERK1/2 activation. Neither Gs nor Gi proteins are coupled to the receptor, as GHS did not induce cAMP production nor inhibit forskolin-stimulated cAMP accumulation in the sbGHSR-1a bearing cells. Furthermore, the ability of the GHSR antagonist D-Lys(3)-GHRP-6 to inhibit basal PLC and basal ERK1/2 activity suggests that this compound is an inverse agonist. In summary, the sbGHSR-1a appears to couple through the Gq/11-mediated pathway to activate PLC, resulting in increased IP3 production and Ca2+ mobilization from both intracellular and extracellular stores. Moreover, sbGHSR-1a may trigger multiple signal transduction cascades to exert its physiological functions. © 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. | - |
dc.language | eng | - |
dc.relation.ispartof | FEBS Letters | - |
dc.subject | Acanthopagrus schlegeli | - |
dc.subject | Black seabream | - |
dc.subject | Functional expression in cultured eukaryotic cell | - |
dc.subject | Growth hormone secretagogue receptor | - |
dc.subject | Signal transduction | - |
dc.title | Signal transduction mechanism of the seabream growth hormone secretagogue receptor | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.febslet.2004.08.088 | - |
dc.identifier.pmid | 15527776 | - |
dc.identifier.scopus | eid_2-s2.0-7544230057 | - |
dc.identifier.volume | 577 | - |
dc.identifier.issue | 1-2 | - |
dc.identifier.spage | 147 | - |
dc.identifier.epage | 153 | - |
dc.identifier.isi | WOS:000225128600025 | - |
dc.identifier.issnl | 0014-5793 | - |