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Article: Over-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity

TitleOver-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity
Authors
KeywordsERK1/2
GHS-R1b
Ghrelin receptors
Ghrelin
Issue Date2007
Citation
International Journal of Biochemistry and Cell Biology, 2007, v. 39, n. 4, p. 752-764 How to Cite?
AbstractIn addition to regulating growth hormone release from the pituitary, ghrelin receptors also influence cell proliferation and apoptosis. By studying mitogen-activated protein kinase activity in human embryonic kidney 293 cells over-expressing ghrelin receptors, we aimed to identify the specific cell signalling pathways used by ghrelin receptors, and to determine if the truncated ghrelin receptor polypeptide had any influence on the functional activity of ghrelin receptors. We found that ghrelin activated extracellular signal-regulated kinases 1/2 with an EC50 value of 10 nM, and that this response was inhibited by the ghrelin receptor antagonists d-Lys(3)-GHRP-6 and [d-Arg1,d-Phe5,d-Trp7,9,Leu11 ]-substance P. Ghrelin had little or no effect on the activity of c-Jun N-terminal kinase, p38 kinase or Akt. Ghrelin appeared to activate extracellular signal-regulated kinases 1/2 through a calcium-independent novel protein kinase C isoform which may utilize diacylglycerol derived from hydrolysis of phosphatidylcholine rather than from phosphatidylinositol. Ghrelin-stimulated extracellular signal-regulated kinases 1/2 activity was independent of transactivation of epidermal growth factor receptors, and even when ghrelin receptor internalization was blocked by concanavalin A or a β-arrestin mutant, there was no decrease in phosphorylated extracellular signal-regulated kinases 1/2, suggesting this is a G protein-dependent process. The truncated ghrelin receptor polypeptide had no effect on ghrelin receptor signalling to extracellular signal-regulated kinases 1/2, but decreased the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors. In conclusion, our results suggest that any up-regulation of the truncated ghrelin receptor polypeptide might preferentially attenuate functional activity dependent on the constitutive activation of ghrelin receptors, while leaving ghrelin-dependent signalling unaffected. © 2006 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/225029
ISSN
2015 Impact Factor: 3.905
2015 SCImago Journal Rankings: 2.003

 

DC FieldValueLanguage
dc.contributor.authorChu, Kit Man-
dc.contributor.authorChow, Kevin B S-
dc.contributor.authorLeung, Po Ki-
dc.contributor.authorLau, Pui Ngan-
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorCheng, Christopher H K-
dc.contributor.authorWise, Helen-
dc.date.accessioned2016-04-18T11:16:33Z-
dc.date.available2016-04-18T11:16:33Z-
dc.date.issued2007-
dc.identifier.citationInternational Journal of Biochemistry and Cell Biology, 2007, v. 39, n. 4, p. 752-764-
dc.identifier.issn1357-2725-
dc.identifier.urihttp://hdl.handle.net/10722/225029-
dc.description.abstractIn addition to regulating growth hormone release from the pituitary, ghrelin receptors also influence cell proliferation and apoptosis. By studying mitogen-activated protein kinase activity in human embryonic kidney 293 cells over-expressing ghrelin receptors, we aimed to identify the specific cell signalling pathways used by ghrelin receptors, and to determine if the truncated ghrelin receptor polypeptide had any influence on the functional activity of ghrelin receptors. We found that ghrelin activated extracellular signal-regulated kinases 1/2 with an EC50 value of 10 nM, and that this response was inhibited by the ghrelin receptor antagonists d-Lys(3)-GHRP-6 and [d-Arg1,d-Phe5,d-Trp7,9,Leu11 ]-substance P. Ghrelin had little or no effect on the activity of c-Jun N-terminal kinase, p38 kinase or Akt. Ghrelin appeared to activate extracellular signal-regulated kinases 1/2 through a calcium-independent novel protein kinase C isoform which may utilize diacylglycerol derived from hydrolysis of phosphatidylcholine rather than from phosphatidylinositol. Ghrelin-stimulated extracellular signal-regulated kinases 1/2 activity was independent of transactivation of epidermal growth factor receptors, and even when ghrelin receptor internalization was blocked by concanavalin A or a β-arrestin mutant, there was no decrease in phosphorylated extracellular signal-regulated kinases 1/2, suggesting this is a G protein-dependent process. The truncated ghrelin receptor polypeptide had no effect on ghrelin receptor signalling to extracellular signal-regulated kinases 1/2, but decreased the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors. In conclusion, our results suggest that any up-regulation of the truncated ghrelin receptor polypeptide might preferentially attenuate functional activity dependent on the constitutive activation of ghrelin receptors, while leaving ghrelin-dependent signalling unaffected. © 2006 Elsevier Ltd. All rights reserved.-
dc.languageeng-
dc.relation.ispartofInternational Journal of Biochemistry and Cell Biology-
dc.subjectERK1/2-
dc.subjectGHS-R1b-
dc.subjectGhrelin receptors-
dc.subjectGhrelin-
dc.titleOver-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biocel.2006.11.007-
dc.identifier.pmid17169600-
dc.identifier.scopuseid_2-s2.0-33847716287-
dc.identifier.volume39-
dc.identifier.issue4-
dc.identifier.spage752-
dc.identifier.epage764-

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