RGD Reference Report - Sub-picomolar relaxin signalling by a pre-assembled RXFP1, AKAP79, AC2, beta-arrestin 2, PDE4D3 complex. - Rat Genome Database

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Sub-picomolar relaxin signalling by a pre-assembled RXFP1, AKAP79, AC2, beta-arrestin 2, PDE4D3 complex.

Authors: Halls, ML  Cooper, DM 
Citation: Halls ML and Cooper DM, EMBO J. 2010 Aug 18;29(16):2772-87. doi: 10.1038/emboj.2010.168. Epub 2010 Jul 27.
RGD ID: 8553331
Pubmed: PMID:20664520   (View Abstract at PubMed)
PMCID: PMC2924647   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2010.168   (Journal Full-text)

Biochemical studies suggest that G-protein-coupled receptors (GPCRs) achieve exquisite signalling specificity by forming selective complexes, termed signalosomes. Here, using cAMP biosensors in single cells, we uncover a pre-assembled, constitutively active GPCR signalosome, that couples the relaxin receptor, relaxin family peptide receptor 1 (RXFP1), to cAMP following receptor stimulation with sub-picomolar concentrations of peptide. The physiological effects of relaxin, a pleiotropic hormone with therapeutic potential in cancer metastasis and heart failure, are generally attributed to local production of the peptide, that occur in response to sub-micromolar concentrations. The highly sensitive signalosome identified here provides a regulatory mechanism for the extremely low levels of relaxin that circulate. The signalosome includes requisite Galpha(s), Gbetagamma and adenylyl cyclase 2 (AC2); AC2 is functionally coupled to RXFP1 through AKAP79 binding to helix 8 of the receptor; activation of AC2 is tonically opposed by protein kinase A (PKA)-activated PDE4D3, scaffolded through a beta-arrestin 2 interaction with Ser(704) of the receptor C-terminus. This elaborate, pre-assembled, ligand-independent GPCR signalosome represents a new paradigm in GPCR signalling and provides a mechanism for the distal actions of low circulating levels of relaxin.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q08499-28553331PMID:20664520IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Adcy2  (adenylate cyclase 2)


Additional Information