Cited 65 times in
Protein kinase C phosphorylation of the metabotropic glutamate receptor mGluR5 on serine 839 regulates Ca2+ oscillations
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김철훈 | - |
dc.date.accessioned | 2015-08-26T16:41:37Z | - |
dc.date.available | 2015-08-26T16:41:37Z | - |
dc.date.issued | 2005 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114920 | - |
dc.description.abstract | The activation of Group 1 metabotropic glutamate receptors, mGluR5 and mGluR1alpha, triggers intracellular calcium release; however, mGluR5 activation is unique in that it elicits Ca2+ oscillations. A short region of the mGluR5 C terminus is the critical determinant and differs from the analogous region of mGluR1alpha by a single amino acid residue, Thr-840, which is an aspartic acid (Asp-854) in mGluR1alpha. Previous studies show that mGluR5-elicited Ca2+ oscillations require protein kinase C (PKC)-dependent phosphorylation and identify Thr-840 as the phosphorylation site. However, direct phosphorylation of mGluR5 has not been studied in detail. We have used biochemical analyses to directly investigate the phosphorylation of the mGluR5 C terminus. We showed that Ser-839 on mGluR5 is directly phosphorylated by PKC, whereas Thr-840 plays a permissive role. Although Ser-839 is conserved in mGluR1alpha (Ser-853), it is not phosphorylated, as the adjacent residue (Asp-854) is not permissive; however, mutagenesis of Asp-854 to a permissive alanine residue allows phosphorylation of Ser-853 on mGluR1alpha. We investigated the physiological consequences of mGluR5 Ser-839 phosphorylation using Ca2+ imaging. Mutations that eliminate Ser-839 phosphorylation prevent the characteristic mGluR5-dependent Ca2+ oscillations. However, mutation of Thr-840 to alanine, which prevents potential Thr-840 phosphorylation but is still permissive for Ser-839 phosphorylation, has no effect on Ca2+ oscillations. Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 25409~25415 | - |
dc.relation.isPartOf | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Amino Acid Sequence | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antibodies | - |
dc.subject.MESH | Calcium Signaling/physiology* | - |
dc.subject.MESH | HeLa Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Molecular Sequence Data | - |
dc.subject.MESH | Mutagenesis, Site-Directed | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Protein Kinase C/metabolism* | - |
dc.subject.MESH | Rabbits | - |
dc.subject.MESH | Receptor, Metabotropic Glutamate 5 | - |
dc.subject.MESH | Receptors, Metabotropic Glutamate/genetics | - |
dc.subject.MESH | Receptors, Metabotropic Glutamate/immunology | - |
dc.subject.MESH | Receptors, Metabotropic Glutamate/metabolism* | - |
dc.subject.MESH | Serine/immunology | - |
dc.subject.MESH | Serine/metabolism | - |
dc.title | Protein kinase C phosphorylation of the metabotropic glutamate receptor mGluR5 on serine 839 regulates Ca2+ oscillations | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학) | - |
dc.contributor.googleauthor | Chul Hoon Kim | - |
dc.contributor.googleauthor | Stephanie Braud | - |
dc.contributor.googleauthor | Katherine W. Roche | - |
dc.contributor.googleauthor | John T. R. Isaac | - |
dc.identifier.doi | 10.1074/jbc.M502644200 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01057 | - |
dc.relation.journalcode | J01258 | - |
dc.identifier.eissn | 1083-351X | - |
dc.identifier.pmid | 15894802 | - |
dc.subject.keyword | 15894802 | - |
dc.contributor.alternativeName | Kim, Chul Hoon | - |
dc.contributor.affiliatedAuthor | Kim, Chul Hoon | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 280 | - |
dc.citation.number | 27 | - |
dc.citation.startPage | 25409 | - |
dc.citation.endPage | 25415 | - |
dc.identifier.bibliographicCitation | JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(27) : 25409-25415, 2005 | - |
dc.identifier.rimsid | 39312 | - |
dc.type.rims | ART | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.