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http://purl.uniprot.org/citations/18435604http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18435604http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18435604http://www.w3.org/2000/01/rdf-schema#comment"FRET (fluorescence resonance energy transfer) and co-immunoprecipitation studies confirmed the capacity of beta-arrestin 2 to self-associate. Amino acids potentially involved in direct protein-protein interaction were identified via combinations of spot-immobilized peptide arrays and mapping of surface exposure. Among potential key amino acids, Lys(285), Arg(286) and Lys(295) are part of a continuous surface epitope located in the polar core between the N- and C-terminal domains. Introduction of K285A/R286A mutations into beta-arrestin 2-eCFP (where eCFP is enhanced cyan fluorescent protein) and beta-arrestin 2-eYFP (where eYFP is enhanced yellow fluorescent protein) constructs substantially reduced FRET, whereas introduction of a K295A mutation had a more limited effect. Neither of these mutants was able to promote beta2-adrenoceptor-mediated phosphorylation of the ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs (mitogen-activated protein kinases). Both beta-arrestin 2 mutants displayed limited capacity to co-immunoprecipitate ERK1/2 and further spot-immobilized peptide arrays indicated each of Lys(285), Arg(286) and particularly Lys(295) to be important for this interaction. Direct interactions between beta-arrestin 2 and the beta2-adrenoceptor were also compromised by both K285A/R286A and K295A mutations of beta-arrestin 2. These were not non-specific effects linked to improper folding of beta-arrestin 2 as limited proteolysis was unable to distinguish the K285A/R286A or K295A mutants from wild-type beta-arrestin 2, and the interaction of beta-arrestin 2 with JNK3 (c-Jun N-terminal kinase 3) was unaffected by the K285A/R286A or L295A mutations. These results suggest that amino acids important for self-association of beta-arrestin 2 also play an important role in the interaction with both the beta2-adrenoceptor and the ERK1/2 MAPKs. Regulation of beta-arrestin 2 self-association may therefore control beta-arrestin 2-mediated beta2-adrenoceptor-ERK1/2 MAPK signalling."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.org/dc/terms/identifier"doi:10.1042/bj20080685"xsd:string
http://purl.uniprot.org/citations/18435604http://purl.org/dc/terms/identifier"doi:10.1042/bj20080685"xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Kolch W."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Kolch W."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Milligan G."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Milligan G."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Houslay M.D."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Houslay M.D."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Baillie G.S."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Baillie G.S."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Adams D.R."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Adams D.R."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Bhari N."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Bhari N."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Houslay T.M."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Houslay T.M."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Pitt A.M."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Pitt A.M."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Xu T.-R."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/author"Xu T.-R."xsd:string
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18435604http://purl.uniprot.org/core/date"2008"xsd:gYear
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