Arrestin Binding to the G Protein-coupled N-Formyl Peptide Receptor Is Regulated by the Conserved “DRY” Sequence

Bennett, Teresa; Maestas, Diane C.; Prossnitz, Eric R.

doi:10.1074/jbc.c000314200

Cited by 70 publications

(68 citation statements)

References 29 publications

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“…2B). Consistent with this finding, mutation in the Arg residue of E͞DRY motif in the N-formyl peptide receptor has also been shown to abolish G protein coupling (19 1A receptors, we used confocal microscopy to monitor translocation of ␤-arrestin 2-GFP to receptors on agonist treatment. When ␤-arrestin 2-GFP was coexpressed with the wildtype AT 1A receptor or the DRY͞AAY mutant receptor, ␤-arrestin 2-GFP was distributed uniformly in the cytoplasm of cells (Fig.…”

Section: Resultsmentioning

confidence: 54%

Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Wei

Ahn

Shenoy

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

622

589

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(maximum stimulation Ϸ50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular ␤-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1͞2 activation with Ϸ60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular ␤-arrestin 2 by small interfering RNA (␤-arrestin dependent). These findings imply the existence of independent G protein-and ␤-arrestin 2-mediated pathways leading to ERK1͞2 activation and the existence of distinct ''active'' conformations of a seven-membrane-spanning receptor coupled to each.

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Section: Resultsmentioning

confidence: 54%

Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Wei

Ahn

Shenoy

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

622

589

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“…1). The receptor contains a short N terminus, seven distinct hydrophobic membrane-spanning domains, and the highly conserved DRY motif located at the interface between the third transmembrane helix and the cytoplasm (20). The receptor has only one initiator methionine in the open reading frame, which contrasts with three such putative initiator methionines in MCH 1 .…”

Section: Resultsmentioning

confidence: 93%

Molecular Cloning and Functional Characterization of MCH2, a Novel Human MCH Receptor

Hill¹,

Duckworth²,

Murdock³

et al. 2001

Journal of Biological Chemistry

219

144

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Melanin-concentrating hormone (MCH) is involved in the regulation of feeding and energy homeostasis. Recently, a 353-amino acid splice variant form of the human orphan receptor SLC-1 (1) (hereafter referred to as MCH 1 ) was identified as an MCH receptor. This report describes the cloning and functional characterization of a novel second human MCH receptor, which we designate MCH 2 , initially identified in a genomic survey sequence as being homologous to MCH 1 receptors. Using this sequence, a full-length cDNA was generated with an open reading frame of 1023 base pairs, encoding a polypeptide of 340 amino acids, with 38% identity to MCH 1 and with many of the structural features conserved in G protein-coupled receptors. This newly discovered receptor belongs to class 1 (rhodopsin-like) of the G protein-coupled receptor superfamily. HEK293 cells transfected with MCH 2 receptors responded to nanomolar concentrations of MCH with an increase in intracellular Ca 2؉ levels and increased cellular extrusion of protons. In addition, fluorescently labeled MCH bound with nanomolar affinity to these cells. The tissue localization of MCH 2 receptor mRNA, as determined by quantitative reverse transcription-polymerase chain reaction, was similar to that of MCH 1 in that both receptors are expressed predominantly in the brain. The discovery of a novel MCH receptor represents a new potential drug target and will allow the further elucidation of MCH-mediated responses. Melanin-concentrating hormone (MCH)1 is a cyclic neuropeptide that was first discovered in teleost fish, in which it acts as a skin color-regulating hormone (2). In rodents its tissue distribution in the perikarya of the lateral hypothalamus and the zona incerta suggests that MCH may be involved in a variety of behavioral responses (3). Similar tissue distributions have been reported in both bird (4) and monkey (5). Reports implicating MCH in the regulation of feeding behavior show that increased food intake occurs after direct administration of MCH into the brain (6) and that MCH is up-regulated after fasting and in obese leptin-deficient mice (7). There are also reports that suggest MCH may be involved in aggressive behavior, anxiety, and reproductive function (8, 9).Recently, several groups independently identified a 353-amino acid splice variant of the orphan G protein-coupled receptor (GPCR) SLC-1 (1) as an MCH receptor (10 -14). In view of the findings of the current study, we propose that this form of SLC-1 be hereafter referred to as MCH 1 . Southern blot and related studies have indicated the absence of additional MCH receptor subtypes that closely resemble MCH 1 at the DNA level (3, 10, 15). However, because degeneracy in receptor-ligand pairings throughout the GPCR superfamily is common, we reasoned that other MCH receptors with low homology to the MCH 1 receptor may exist. This suggestion is supported by reports of pharmacological differences between the MCH 1 receptor and MCH binding sites in various cell lines and tissues (10).Sequencing of the human...

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“…This suggested that our methods would be amenable to a receptor-arrestin study. The FPR colocalizes with arrestin-2 and arrestin-3 in U937 cells transfected to express the FPR and in neutrophils (30). 2 The addition of wild-type arrestin-3 had no effect on the ligand dissociation rate or sensitivity to guanine nucleotide (Fig.…”

Section: Resultsmentioning

confidence: 99%

Real-time Analysis of G Protein-coupled Receptor Reconstitution in a Solubilized System

Bennett

Key²,

Gurevich

et al. 2001

Journal of Biological Chemistry

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Arrestin Binding to the G Protein-coupled N-Formyl Peptide Receptor Is Regulated by the Conserved “DRY” Sequence

Cited by 70 publications

References 29 publications

Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Molecular Cloning and Functional Characterization of MCH2, a Novel Human MCH Receptor

Real-time Analysis of G Protein-coupled Receptor Reconstitution in a Solubilized System

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