| http://purl.uniprot.org/citations/18534983 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18534983 | http://www.w3.org/2000/01/rdf-schema#comment | "Members of the seven-transmembrane receptor (7TMR) superfamily are sequestered from the plasma membrane following stimulation both to limit cellular responses as well as to initiate novel G protein-independent signaling pathways. The best studied mechanism for 7TMR internalization is via clathrin-coated pits, where clathrin and adaptor protein complex 2 nucleate and polymerize upon encountering the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) to form the outer layer of the clathrin-coated vesicle. Activated receptors are recruited to clathrin-coated pits by beta-arrestins, scaffolding proteins that interact with agonist-occupied 7TMRs as well as adaptor protein complex 2 and clathrin. We report here that following stimulation of the beta2-adrenergic receptor (beta2-AR), a prototypical 7TMR, beta-arrestins bind phosphatidylinositol 4-phosphate 5-kinase (PIP5K) Ialpha, a PIP(2)-producing enzyme. Furthermore, beta-arrestin2 is required to form a complex with PIP5K Ialpha and agonist-occupied beta2-AR, and beta-arrestins synergize with the kinase to produce PIP(2) in response to isoproterenol stimulation. Interestingly, beta-arrestins themselves bind PIP(2), and a beta-arrestin mutant deficient in PIP(2) binding no longer internalizes 7TMRs, fails to interact with PIP5K Ialpha, and is not associated with PIP kinase activity assayed in vitro. However, a chimeric protein in which the core kinase domain of PIP5K Ialpha has been fused to the same beta-arrestin mutant rescues internalization of beta2-ARs. Collectively, these data support a model in which beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m800431200"xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/author | "Lefkowitz R.J."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/author | "Nelson C.D."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/author | "Whalen E.J."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/author | "Kovacs J.J."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/author | "Nobles K.N."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/pages | "21093-21101"xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/title | "Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor."xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://purl.uniprot.org/core/volume | "283"xsd:string |
| http://purl.uniprot.org/citations/18534983 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18534983 |
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