RGD Reference Report - Proteomic analysis of beta1-adrenergic receptor interactions with PDZ scaffold proteins. - Rat Genome Database

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Proteomic analysis of beta1-adrenergic receptor interactions with PDZ scaffold proteins.

Authors: He, J  Bellini, M  Inuzuka, H  Xu, J  Xiong, Y  Yang, X  Castleberry, AM  Hall, RA 
Citation: He J, etal., J Biol Chem. 2006 Feb 3;281(5):2820-7. Epub 2005 Nov 29.
RGD ID: 8553792
Pubmed: PMID:16316992   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M509503200   (Journal Full-text)

Many G protein-coupled receptors possess carboxyl-terminal motifs ideal for interaction with PDZ scaffold proteins, which can control receptor trafficking and signaling in a cell-specific manner. To gain a panoramic view of beta1-adrenergic receptor (beta AR) interactions with PDZ scaffolds, the beta1AR carboxyl terminus was screened against a newly developed proteomic array of PDZ domains. These screens confirmed beta1AR associations with several previously identified PDZ partners, such as PSD-95, MAGI-2, GIPC, and CAL. Moreover, two novel beta1AR-interacting proteins, SAP97 and MAGI-3, were also identified. The beta1AR carboxyl terminus was found to bind specifically to the first PDZ domain of MAGI-3, with the last four amino acids (E-S-K-V) of beta1AR being the key determinants of the interaction. Full-length beta1AR robustly associated with full-length MAGI-3 in cells, and this association was abolished by mutation of the beta1AR terminal valine residue to alanine (V477A), as determined by co-immunoprecipitation experiments and immunofluorescence co-localization studies. MAGI-3 co-expression with beta1AR profoundly impaired beta1AR-mediated ERK1/2 activation but had no apparent effect on beta1AR-mediated cyclic AMP generation or agonist-promoted beta1AR internalization. These findings revealed that the interaction of MAGI-3 with beta1AR can selectively regulate specific aspects of receptor signaling. Moreover, the screens of the PDZ domain proteomic array provide a comprehensive view of beta1AR interactions with PDZ scaffolds, thereby shedding light on the molecular mechanisms by which beta1 AR signaling and trafficking can be regulated in a cell-specific manner.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adrb1Ratprotein binding enablesIPIUniProtKB:Q9JK71PMID:16316992IntAct 
Dlg4Ratprotein binding enablesIPIUniProtKB:P08588PMID:16316992IntAct 
Magi3Ratprotein binding enablesIPIUniProtKB:P18090PMID:16316992IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Adrb1  (adrenoceptor beta 1)
Dlg4  (discs large MAGUK scaffold protein 4)
Magi3  (membrane associated guanylate kinase, WW and PDZ domain containing 3)


Additional Information