| http://purl.uniprot.org/citations/12860966 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12860966 | http://www.w3.org/2000/01/rdf-schema#comment | "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 PLCbeta 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 PLCbeta in pancreatic acini and brain extracts and stimulated GAP activity of RGS4 and of PLCbeta in an in vitro reconstitution system, with minimal effect on PLCbeta-mediated PIP2 hydrolysis. These findings describe a novel, unexpected function of Homer proteins, demonstrate that RGS proteins and PLCbeta 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."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.org/dc/terms/identifier | "doi:10.1083/jcb.200210109"xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Luo X."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Muallem S."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Kang S.H."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Ross E.M."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Tu J."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Worley P.F."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Dehoff M."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Shin D.M."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/author | "Nayak S.K."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/name | "J Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/pages | "293-303"xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/title | "Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities."xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://purl.uniprot.org/core/volume | "162"xsd:string |
| http://purl.uniprot.org/citations/12860966 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12860966 |
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