DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, You-Me | ko |
dc.contributor.author | Benovic, JL | ko |
dc.date.accessioned | 2018-03-21T02:57:41Z | - |
dc.date.available | 2018-03-21T02:57:41Z | - |
dc.date.created | 2018-03-14 | - |
dc.date.created | 2018-03-14 | - |
dc.date.issued | 2002-08 | - |
dc.identifier.citation | JOURNAL OF BIOLOGICAL CHEMISTRY, v.277, no.34, pp.30760 - 30768 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240870 | - |
dc.description.abstract | The non-visual arrestins, arrestin-2 and arrestin-3, play a critical role in regulating the signaling and trafficking of many G protein-coupled receptors (GPCRs). Molecular insight into the role of arrestins in GPCR trafficking has suggested that arrestin interaction with clathrin, beta(2)-adaptin (the beta-subunit of the adaptor protein AP2), and phosphoinositides contributes to this process. In the present study, we have attempted to better define the molecular basis and functional role of arrestin-2 interaction with clathrin and beta(2)-adaptin. Site-directed mutagenesis revealed that the C-terminal region of arrestin-2 mediated beta(2)-adaptin and clathrin interaction with Phe-391 and Arg-395 having an essential role in beta(2)-adaptin binding and LIELD (residues 376-380) having an essential role in clathrin binding. Interestingly, arrestin-2-R169E, an activated form of arrestin that binds to GPCRs in a phosphorylation-independent manner, has significantly enhanced binding to beta(2)-adaptin and clathrin. This suggests that receptor-induced conformational changes in the C-terminal tail of arrestin-2 will likely play a major role in mediating arrestin interaction with clathrin-coated pits. In an effort to clarify the role of these interactions in GPCR trafficking we generated arrestin mutants that were completely and selectively defective in either clathrin (arrestin-2-DeltaLIELD) or beta(2)-adaptin (arrestin-2-F391A) interaction. Analysis of these mutants in COS-1 cells revealed that arrestin/clathrin interaction was essential for agonist-promoted internalization of the beta(2)-adrenergic receptor, while arrestin/beta(2)-adaptin interaction appeared less critical. Arrestin-2 mutants defective in both clathrin and beta(2)-adaptin binding functioned as effective dominant negatives in HEK293 cells and significantly attenuated beta(2)-adrenergic receptor internalization. These mutants should prove useful in better defining the role of arrestins in mediating receptor trafficking. | - |
dc.language | English | - |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | - |
dc.subject | BETA-ARRESTIN | - |
dc.subject | BETA(2)-ADRENERGIC RECEPTOR | - |
dc.subject | ARRESTIN/CLATHRIN INTERACTION | - |
dc.subject | CRYSTAL-STRUCTURE | - |
dc.subject | VISUAL ARRESTIN | - |
dc.subject | 48-KDA PROTEIN | - |
dc.subject | ENDOCYTOSIS | - |
dc.subject | BINDING | - |
dc.subject | ACTIVATION | - |
dc.subject | INTERNALIZATION | - |
dc.title | Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2 in G protein-coupled receptor trafficking | - |
dc.type | Article | - |
dc.identifier.wosid | 000177579800047 | - |
dc.identifier.scopusid | 2-s2.0-0037163045 | - |
dc.type.rims | ART | - |
dc.citation.volume | 277 | - |
dc.citation.issue | 34 | - |
dc.citation.beginningpage | 30760 | - |
dc.citation.endingpage | 30768 | - |
dc.citation.publicationname | JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.identifier.doi | 10.1074/jbc.M204528200 | - |
dc.contributor.localauthor | Kim, You-Me | - |
dc.contributor.nonIdAuthor | Benovic, JL | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | BETA-ARRESTIN | - |
dc.subject.keywordPlus | BETA(2)-ADRENERGIC RECEPTOR | - |
dc.subject.keywordPlus | ARRESTIN/CLATHRIN INTERACTION | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURE | - |
dc.subject.keywordPlus | VISUAL ARRESTIN | - |
dc.subject.keywordPlus | 48-KDA PROTEIN | - |
dc.subject.keywordPlus | ENDOCYTOSIS | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | INTERNALIZATION | - |
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