Cited 79 times in
Homer 2 tunes G protein–coupled receptors stimulus intensity by regulating RGS proteins and PLCβ GAP activities
DC Field | Value | Language |
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dc.contributor.author | 신동민 | - |
dc.date.accessioned | 2015-07-15T17:15:37Z | - |
dc.date.available | 2015-07-15T17:15:37Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0021-9525 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114551 | - |
dc.description.abstract | Homers are scaffolding proteins that bind G protein–coupled receptors (GPCRs), inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs), ryanodine receptors, and TRP channels. However, their role in Ca2+ signaling in vivo is not known. Characterization of Ca2+ signaling in pancreatic acinar cells from Homer2−/− and Homer3−/− mice showed that Homer 3 has no discernible role in Ca2+ signaling in these cells. In contrast, we found that Homer 2 tunes intensity of Ca2+ signaling by GPCRs to regulate the frequency of [Ca2+]i oscillations. Thus, deletion of Homer 2 increased stimulus intensity by increasing the potency for agonists acting on various GPCRs to activate PLCβ and evoke Ca2+ release and oscillations. This was not due to aberrant localization of IP3Rs in cellular microdomains or IP3R channel activity. Rather, deletion of Homer 2 reduced the effectiveness of exogenous regulators of G proteins signaling proteins (RGS) to inhibit Ca2+ signaling in vivo. Moreover, Homer 2 preferentially bound to PLCβ in pancreatic acini and brain extracts and stimulated GAP activity of RGS4 and of PLCβ in an in vitro reconstitution system, with minimal effect on PLCβ-mediated PIP2 hydrolysis. These findings describe a novel, unexpected function of Homer proteins, demonstrate that RGS proteins and PLCβ GAP activities are regulated functions, and provide a molecular mechanism for tuning signal intensity generated by GPCRs and, thus, the characteristics of [Ca2+]i oscillations. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 293~303 | - |
dc.relation.isPartOf | JOURNAL OF CELL BIOLOGY | - |
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 | Animals | - |
dc.subject.MESH | Bombesin/pharmacology | - |
dc.subject.MESH | Calcium/metabolism | - |
dc.subject.MESH | Calcium/pharmacokinetics | - |
dc.subject.MESH | Calcium Signaling | - |
dc.subject.MESH | Calcium-Transporting ATPases/antagonists & inhibitors | - |
dc.subject.MESH | Calcium-Transporting ATPases/metabolism | - |
dc.subject.MESH | Carbachol/pharmacology | - |
dc.subject.MESH | Carrier Proteins/chemistry | - |
dc.subject.MESH | Carrier Proteins/genetics | - |
dc.subject.MESH | Carrier Proteins/metabolism* | - |
dc.subject.MESH | Cholecystokinin/pharmacology | - |
dc.subject.MESH | Cholinergic Agonists/pharmacology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology | - |
dc.subject.MESH | GTP-Binding Proteins/agonists | - |
dc.subject.MESH | GTP-Binding Proteins/metabolism* | - |
dc.subject.MESH | GTPase-Activating Proteins/metabolism* | - |
dc.subject.MESH | Gene Deletion | - |
dc.subject.MESH | Homer Scaffolding Proteins | - |
dc.subject.MESH | Indoles/pharmacology | - |
dc.subject.MESH | Isoenzymes/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Neuropeptides/chemistry | - |
dc.subject.MESH | Neuropeptides/genetics | - |
dc.subject.MESH | Neuropeptides/metabolism* | - |
dc.subject.MESH | Pancreas/cytology | - |
dc.subject.MESH | Pancreas/drug effects | - |
dc.subject.MESH | Pancreas/metabolism | - |
dc.subject.MESH | Phosphatidylinositol 4,5-Diphosphate/metabolism | - |
dc.subject.MESH | Phospholipase C beta | - |
dc.subject.MESH | Protein Isoforms/genetics | - |
dc.subject.MESH | Protein Isoforms/metabolism | - |
dc.subject.MESH | RGS Proteins/metabolism* | - |
dc.subject.MESH | Sarcoplasmic Reticulum Calcium-Transporting ATPases | - |
dc.subject.MESH | Type C Phospholipases/metabolism* | - |
dc.title | Homer 2 tunes G protein–coupled receptors stimulus intensity by regulating RGS proteins and PLCβ GAP activities | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학) | - |
dc.contributor.googleauthor | Dong Min Shin | - |
dc.contributor.googleauthor | Marlin Dehoff | - |
dc.contributor.googleauthor | Shmuel Muallem | - |
dc.contributor.googleauthor | Paul F. Worley | - |
dc.contributor.googleauthor | Elliott M. Ross | - |
dc.contributor.googleauthor | Surendra K. Nayak | - |
dc.contributor.googleauthor | Jiangchen Tu | - |
dc.contributor.googleauthor | Shin Hyeok Kang | - |
dc.contributor.googleauthor | Xiang Luo | - |
dc.identifier.doi | 10.1083/jcb.200210109 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02091 | - |
dc.relation.journalcode | J01300 | - |
dc.identifier.eissn | 1540-8140 | - |
dc.identifier.pmid | 12860966 | - |
dc.subject.keyword | 12860966 | - |
dc.contributor.alternativeName | Shin, Dong Min | - |
dc.contributor.affiliatedAuthor | Shin, Dong Min | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 162 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 293 | - |
dc.citation.endPage | 303 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CELL BIOLOGY, Vol.162(2) : 293-303, 2003 | - |
dc.identifier.rimsid | 44456 | - |
dc.type.rims | ART | - |
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