Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors

Cen, Bo; Xiong, Ying; Ma, Lan; Pei, Gang

doi:10.1124/mol.59.4.758

Cited by 66 publications

(59 citation statements)

References 40 publications

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“…Although phosphorylation of the C-tail appears to be required for high affinity binding of ␤-arrestins (2, 3), several receptors have been reported to interact with ␤-arrestins through the third intracellular loop. For example, both the third intracellular loop and the C-tail are important for ␤-arrestin binding to the neurokinin receptor 1 (23), delta opioid receptor (24,25), and lutropin/choriogonadotropin receptor (26). In each case, Ser/Thr residues in the third intracellular loop also appear to be critical for ␤-arrestin binding.…”

Section: Resultsmentioning

confidence: 99%

Stable Interaction between β-Arrestin 2 and Angiotensin Type 1A Receptor Is Required for β-Arrestin 2-mediated Activation of Extracellular Signal-regulated Kinases 1 and 2

Wei

Ahn

Barnes

et al. 2004

Journal of Biological Chemistry

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Binding of ␤-arrestins to seven-membrane-spanning receptors (7MSRs) not only leads to receptor desensitization and endocytosis but also elicits additional signaling processes. We recently proposed that stimulation of the angiotensin type 1A (AT 1A ) receptor results in independent ␤-arrestin 2-and G protein-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. Here we utilize two AT 1A mutant receptors to study these independent pathways, one truncated at residue 324, thus removing all potential carboxyl-terminal phosphorylation sites, and the other bearing four mutations in the serine/threonine-rich clusters in the carboxyl terminus. As assessed by confocal microscopy, the two mutant receptors interacted with ␤-arrestin 2-green fluorescent protein with much lower affinity than did the wild-type receptor. In addition, the mutant receptors more robustly stimulated G protein-mediated inositol phosphate production. Approximately one-half of the wild-type AT 1A receptor-stimulated ERK1/2 activation was via a ␤-arrestin 2-dependent pathway (suppressed by ␤-arrestin 2 small interfering RNA), whereas the rest was mediated by a G protein-dependent pathway (suppressed by protein kinase C inhibitor). ERK1/2 activation by the mutant receptors was insensitive to ␤-arrestin 2 small interfering RNA but was reduced more than 80% by a protein kinase C inhibitor. The biochemical consequences of ERK activation by the G protein and ␤-arrestin 2-dependent pathways were also distinct. Gprotein-mediated ERK activation enhanced the transcription of early growth response 1, whereas ␤-arrestin 2-dependent ERK activation did not. In addition, stimulation of the truncated AT 1A mutant receptor caused significantly greater early growth response 1 transcription than did the wild-type receptor. These findings demonstrate how the ability of receptors to interact with ␤-arrestins determines both the mechanism of ERK activation as well as the physiological consequences of this activation.

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Section: Resultsmentioning

confidence: 99%

Stable Interaction between β-Arrestin 2 and Angiotensin Type 1A Receptor Is Required for β-Arrestin 2-mediated Activation of Extracellular Signal-regulated Kinases 1 and 2

Wei

Ahn

Barnes

et al. 2004

Journal of Biological Chemistry

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“…Rhodopsin i1 and i3 competed with P-Rh* with 30-1000 μM affinities, whereas lutropin receptor i3 had an IC50 of 10 μM (Mukherjee et al, 1999b). The studies of arrestin interactions with receptor elements using surface plasmon resonance also yielded micromolar affinities (Cen et al, 2001a;Liu et al, 2004). Wild-type arrestins bound to the immobilized phosphorylated C-terminal peptide of the N-formyl peptide receptor with micromolar affinities, although several constitutively active mutants demonstrated submicromolar dissociation constants (Potter et al, 2002).…”

Section: Receptor Elements Implicated In Arrestin Bindingmentioning

confidence: 99%

The structural basis of arrestin-mediated regulation of G-protein-coupled receptors

Gurevich

2006

Pharmacology & Therapeutics

410

446

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The 4 mammalian arrestins serve as almost universal regulators of the largest known family of signaling proteins, G-protein-coupled receptors (GPCRs). Arrestins terminate receptor interactions with G proteins, redirect the signaling to a variety of alternative pathways, and orchestrate receptor internalization and subsequent intracellular trafficking. The elucidation of the structural basis and fine molecular mechanisms of the arrestin-receptor interaction paved the way to the targeted manipulation of this interaction from both sides to produce very stable or extremely transient complexes that helped to understand the regulation of many biologically important processes initiated by active GPCRs. The elucidation of the structural basis of arrestin interactions with numerous nonreceptor-binding partners is long overdue. It will allow the construction of fully functional arrestins in which the ability to interact with individual partners is specifically disrupted or enhanced by targeted mutagenesis. These "custom-designed" arrestin mutants will be valuable tools in defining the role of various interactions in the intricate interplay of multiple signaling pathways in the living cell. The identification of arrestin-binding sites for various signaling molecules will also set the stage for designing molecular tools for therapeutic intervention that may prove useful in numerous disorders associated with congenital or acquired disregulation of GPCR signaling.

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“…Because nephrin belongs to the same group of tyrosine phosphorylated type-1 transmembrane-spanning receptors, one can speculate that arrestins also interact with nephrin. In addition, nephrin harbors several potential ␤-arrestin-binding sites with the consensus motif S͞TX 4-5 S͞T (17). The role of arrestins in desensitization of activated seven transmembrane-spanning G protein-coupled receptors is well documented.…”

mentioning

confidence: 99%

β-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity

Quack

Rump

Gerke

et al. 2006

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

100

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␤-Arrestins mediate internalization of plasma membrane receptors. Nephrin, a structural component of the glomerular slit diaphragm, is a single transmembrane spanning receptor and belongs to the family of adhesion molecules. Its mutation causes a hereditary nephrotic syndrome. We report the previously undescribed interaction of ␤-arrestin2 with the nephrin C terminus. The phosphorylation status of nephrin Y1193 regulates inversely the binding of ␤-arrestin2 and podocin. The Src-family member Yes, known to enhance podocin-nephrin interaction by nephrin phosphorylation, diminishes ␤-arrestin2-nephrin interaction. ␤-Arrestin2 induces nephrin endocytosis and attenuates nephrin signaling. This finding suggests that nephrin Y1193 serves as a molecular switch that determines the integrity of the slit diaphragm by functional competition between ␤-arrestin2 and podocin. This concept offers a molecular pathomechanism of slit diaphragm distortion and opens therapeutic avenues for glomerular diseases. glomerular slit diaphragm ͉ signaling ͉ podocin ͉ podocyte

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Direct and Differential Interaction of β-Arrestins with the Intracellular Domains of Different Opioid Receptors

Cited by 66 publications

References 40 publications

Stable Interaction between β-Arrestin 2 and Angiotensin Type 1A Receptor Is Required for β-Arrestin 2-mediated Activation of Extracellular Signal-regulated Kinases 1 and 2

Stable Interaction between β-Arrestin 2 and Angiotensin Type 1A Receptor Is Required for β-Arrestin 2-mediated Activation of Extracellular Signal-regulated Kinases 1 and 2

The structural basis of arrestin-mediated regulation of G-protein-coupled receptors

β-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity

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