Scholars@Duke
Sudha Kaup Shenoy

Sudha Kaup Shenoy

Professor in Medicine
Medicine, Cardiology
skshenoy@dm.duke.edu
Duke Box 102146, Durham, NC 27710
148-A CARL Bldg, Durham, NC 27710

Selected Publications

USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality.

Journal Article Am J Physiol Heart Circ Physiol · November 1, 2024 Left ventricular hypertrophy (LVH) caused by chronic pressure overload with subsequent pathological remodeling is a major cardiovascular risk factor for heart failure and mortality. The role of deubiquitinases in LVH has not been well characterized. To def ... Full text Link to item Cite

β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure.

Journal Article Curr Opin Physiol · February 2024 The lethality of heart failure (HF), particularly in the context of post-acute sequelae SARS-CoV-2 infection (PASC)-related myocarditis, necessitates the discovery of the cellular pathways implicated in cardiovascular disease (CVD). We summarize the signal ... Full text Link to item Cite

How carvedilol does not activate β2-adrenoceptors.

Journal Article Nat Commun · November 30, 2023 Full text Link to item Cite

An insulin-regulated arrestin domain protein controls hepatic glucagon action.

Journal Article J Biol Chem · August 2023 Glucagon signaling is essential for maintaining normoglycemia in mammals. The arrestin fold superfamily of proteins controls the trafficking, turnover, and signaling of transmembrane receptors as well as other intracellular signaling functions. Further inv ... Full text Link to item Cite

Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation.

Journal Article J Biol Chem · July 2023 Reversible lysine-63 (K63) polyubiquitination regulates proinflammatory signaling in vascular smooth muscle cells (SMCs) and plays an integral role in atherosclerosis. Ubiquitin-specific peptidase 20 (USP20) reduces NFκB activation triggered by proinflamma ... Full text Open Access Link to item Cite

The ubiquitination status of the glucagon receptor determines signal bias.

Journal Article J Biol Chem · May 2023 The pancreatic hormone glucagon activates the glucagon receptor (GCGR), a class B seven-transmembrane G protein-coupled receptor that couples to the stimulatory heterotrimeric G protein and provokes PKA-dependent signaling cascades vital to hepatic glucose ... Full text Link to item Cite

A single phenylalanine residue in β-arrestin2 critically regulates its binding to G protein-coupled receptors.

Journal Article J Biol Chem · May 2022 Arrestins and their yeast homologs, arrestin-related trafficking adaptors (ARTs), share a stretch of 29 amino acids called the ART motif. However, the functionality of that motif is unknown. We now report that deleting this motif prevents agonist-induced u ... Full text Link to item Cite

Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.

Journal Article J Biol Chem · December 4, 2020 The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein-coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterizati ... Full text Link to item Cite

Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.

Journal Article J Biol Chem · December 4, 2020 The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein-coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterizati ... Full text Link to item Cite

In-frame fusion of SUMO1 enhances βarrestin2's association with activated GPCRs as well as with nuclear pore complexes.

Journal Article Cell Signal · November 2020 Small ubiquitin like modifier (SUMO) conjugation or SUMOylation of βarrestin2 promotes its association with the clathrin adaptor protein AP2 and facilitates rapid β2 adrenergic receptor (β2AR) internalization. However, disruption of the consensus SUMOylati ... Full text Link to item Cite

SnapShot: β-Arrestin Functions.

Journal Article Cell · September 3, 2020 The arrestins are ubiquitously expressed adaptor proteins that orchestrate transmembrane signaling cascades triggered by the 7-transmembrane G protein-coupled receptors. While originally discovered as proteins that block receptor-G protein coupling, arrest ... Full text Link to item Cite

Encoding the β-Arrestin Trafficking Fate of Ghrelin Receptor GHSR1a: C-Tail-Independent Molecular Determinants in GPCRs.

Journal Article ACS Pharmacol Transl Sci · August 9, 2019 G-protein-coupled receptors (GPCRs) can bias signaling through distinct biochemical pathways that originate from G-protein/receptor and β-arrestin/receptor complexes. Receptor conformations supporting β-arrestin engagement depend on multiple receptor deter ... Full text Link to item Cite

The deubiquitinase ubiquitin-specific protease 20 is a positive modulator of myocardial β1-adrenergic receptor expression and signaling.

Journal Article J Biol Chem · February 15, 2019 Reversible ubiquitination of G protein-coupled receptors regulates their trafficking and signaling; whether deubiquitinases regulate myocardial β1-adrenergic receptors (β1ARs) is unknown. We report that ubiquitin-specific protease 20 (USP20) deubiquitinate ... Full text Link to item Cite

Detection of β-Arrestin-Mediated G Protein-Coupled Receptor Ubiquitination Using BRET.

Journal Article Methods Mol Biol · 2019 Ubiquitination of G protein-coupled receptors (GPCRs) is an important dynamic posttranslational modification that has been linked to the intracellular trafficking of internalized GPCRs to lysosomes. Ubiquitination of GPCRs is mediated by specific E3 ubiqui ... Full text Link to item Cite

Drebrin regulates angiotensin II-induced aortic remodelling.

Journal Article Cardiovasc Res · November 1, 2018 AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebr ... Full text Open Access Link to item Cite

USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis.

Journal Article Arterioscler Thromb Vasc Biol · October 2018 Objective- Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination that activates proteins downstream of proatherogenic receptors. Deubiquitination of these prote ... Full text Link to item Cite

Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9.

Journal Article Sci Signal · September 25, 2018 G protein-coupled receptors (GPCRs) use diverse mechanisms to regulate the mitogen-activated protein kinases ERK1/2. β-Arrestins (βArr1/2) are ubiquitous inhibitors of G protein signaling, promoting GPCR desensitization and internalization and serving as s ... Full text Link to item Cite

GPCR desensitization: Acute and prolonged phases.

Journal Article Cell Signal · January 2018 G protein-coupled receptors (GPCRs) transduce a wide array of extracellular signals and regulate virtually every aspect of physiology. While GPCR signaling is essential, overstimulation can be deleterious, resulting in cellular toxicity or uncontrolled cel ... Full text Link to item Cite

Regulation of inflammation by β-arrestins: Not just receptor tales.

Journal Article Cell Signal · January 2018 The ubiquitously expressed, multifunctional scaffolding proteins β-arrestin1 and β-arrestin2 each affect inflammatory signaling in a variety of cell lines. In addition to binding the carboxyl-terminal tails of innumerable 7-transmembrane receptors, β-arres ... Full text Link to item Cite

Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells.

Journal Article Cardiovasc Res · November 1, 2017 AIMS: Chronic kidney disease (CKD) is a powerful independent risk factor for cardiovascular events, including vein graft failure. Because CKD impairs the clearance of small proteins, we tested the hypothesis that CKD exacerbates vein graft disease by eleva ... Full text Open Access Link to item Cite

Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.

Journal Article JCI Insight · September 7, 2017 The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic receptor (βAR) signaling and endocytosis. Previous studies showed that cardi ... Full text Open Access Link to item Cite

G Protein-Coupled Receptor Signaling Through β-Arrestin-Dependent Mechanisms.

Journal Article J Cardiovasc Pharmacol · September 2017 β-arrestin1 (or arrestin2) and β-arrestin2 (or arrestin3) are ubiquitously expressed cytosolic adaptor proteins that were originally discovered for their inhibitory role in G protein-coupled receptor (GPCR) signaling through heterotrimeric G proteins. Howe ... Full text Link to item Cite

Ubiquitin-Related Roles of β-Arrestins in Endocytic Trafficking and Signal Transduction.

Journal Article J Cell Physiol · October 2016 The non-visual arrestins, β-arrestin1, and β-arrestin2 were originally identified as proteins that bind to seven-transmembrane receptors (7TMRs, also called G protein-coupled receptors, GPCRs) and block heterotrimeric G protein activation, thus leading to ... Full text Link to item Cite

Cover Image, Volume 231, Number 10, October 2016.

Journal Article J Cell Physiol · October 2016 Cover: The cover image, by Sudha K. Shenoy et al., is based on the Mini-Review Ubiquitin-Related Roles of β-Arrestins in Endocytic Trafficking and Signal Transduction, DOI: 10.1002/jcp.25317. ... Full text Link to item Cite

Microgravity induces proteomics changes involved in endoplasmic reticulum stress and mitochondrial protection.

Journal Article Sci Rep · September 27, 2016 On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-define ... Full text Open Access Link to item Cite

Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation.

Journal Article J Biol Chem · April 1, 2016 Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFκB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity ca ... Full text Link to item Cite

Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination.

Journal Article Prog Mol Biol Transl Sci · 2016 β-Arrestin1 and β-arrestin2 are homologous adaptor proteins that are ubiquitously expressed in mammalian cells. They belong to a four-member family of arrestins that regulate the vast family of seven-transmembrane receptors that couple to heterotrimeric G ... Full text Link to item Cite

Preface.

Journal Article Prog Mol Biol Transl Sci · 2016 Full text Link to item Cite

Chapter One - Ubiquitination and Deubiquitination of G Protein-Coupled Receptors.

Journal Article Prog Mol Biol Transl Sci · 2016 The seven-transmembrane containing G protein-coupled receptors (GPCRs) constitute the largest family of cell-surface receptors. Transmembrane signaling by GPCRs is fundamental to many aspects of physiology including vision, olfaction, cardiovascular, and r ... Full text Link to item Cite

PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE Ubiquitination and Transmembrane Signaling

Journal Article UBIQUITINATION AND TRANSMEMBRANE SIGNALING · January 1, 2016 Link to item Cite

Phosphorylation of the deubiquitinase USP20 by protein kinase A regulates post-endocytic trafficking of β2 adrenergic receptors to autophagosomes during physiological stress.

Journal Article J Biol Chem · April 3, 2015 Ubiquitination by the E3 ligase Nedd4 and deubiquitination by the deubiquitinases USP20 and USP33 have been shown to regulate the lysosomal trafficking and recycling of agonist-activated β2 adrenergic receptors (β2ARs). In this work, we demonstrate that, i ... Full text Link to item Cite

Arrestin interaction with E3 ubiquitin ligases and deubiquitinases: functional and therapeutic implications.

Journal Article Handb Exp Pharmacol · 2014 Arrestins constitute a small family of four homologous adaptor proteins (arrestins 1-4), which were originally identified as inhibitors of signal transduction elicited by the seven-transmembrane G protein-coupled receptors. Currently arrestins (especially ... Full text Link to item Cite

Deubiquitinases and their emerging roles in β-arrestin-mediated signaling.

Journal Article Methods Enzymol · 2014 The two homologous mammalian proteins called β-arrestin1 (also known as arrestin2) and β-arrestin2 (also called arrestin3) are now widely accepted as endocytic and signaling adaptors for G protein-coupled receptors (GPCRs), growth factor receptors, and ion ... Full text Link to item Cite

Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking.

Journal Article EMBO Rep · February 2013 β-arrestin 1 and 2 (also known as arrestin 2 and 3) are homologous adaptor proteins that regulate seven-transmembrane receptor trafficking and signalling. Other proteins with predicted 'arrestin-like' structural domains but lacking sequence homology have b ... Full text Link to item Cite

Arrestins and protein ubiquitination.

Journal Article Prog Mol Biol Transl Sci · 2013 The adaptor proteins, β-arrestins 1 and 2, were originally identified as inhibitors of G protein signaling at the seven-transmembrane receptors (7TMRs, also called G protein-coupled receptors or GPCRs). Subsequent studies have established β-arrestins as cr ... Full text Link to item Cite

MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors.

Journal Article J Cell Biol · November 26, 2012 Lysosomal degradation of ubiquitinated β(2)-adrenergic receptors (β(2)ARs) serves as a major mechanism of long-term desensitization in response to prolonged agonist stimulation. Surprisingly, the βAR antagonist carvedilol also induced ubiquitination and ly ... Full text Link to item Cite

G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors.

Journal Article Arterioscler Thromb Vasc Biol · February 2012 OBJECTIVE: G protein-coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-κB (NF-κB). This study sought to determine whether and by what mechanisms GRK ... Full text Open Access Link to item Cite

β-arrestin1 mediates metastatic growth of breast cancer cells by facilitating HIF-1-dependent VEGF expression.

Journal Article Oncogene · January 19, 2012 Featured Publication β-Arrestins 1 and 2 are multifunctional adaptor proteins originally discovered for their role in desensitizing seven-transmembrane receptor signaling via the heterotrimeric guanine nucleotide-binding proteins. Recently identified roles of β-arrestins inclu ... Full text Link to item Cite

β-Arrestin and dishevelled coordinate biased signaling.

Journal Article Proc Natl Acad Sci U S A · December 13, 2011 Full text Link to item Cite

β-Arrestin-mediated receptor trafficking and signal transduction.

Journal Article Trends Pharmacol Sci · September 2011 β-Arrestins function as endocytic adaptors and mediate trafficking of a variety of cell-surface receptors, including seven-transmembrane receptors (7TMRs). In the case of 7TMRs, β-arrestins carry out these tasks while simultaneously inhibiting upstream G-p ... Full text Link to item Cite

A tale of two sites: How ubiquitination of a G protein-coupled receptor is coupled to its lysosomal trafficking from distinct receptor domains.

Journal Article Commun Integr Biol · September 2011 The β(2)-adrenergic receptor (β(2)AR) is a prototypical G(s)-coupled receptor belonging to the superfamily of seven transmembrane spanning heptahelical receptors (7TMRs or G protein-coupled receptors [GPCRs])-therapeutically the most diverse and accessible ... Full text Link to item Cite

A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.

Journal Article Nature · August 21, 2011 The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is gene ... Full text Link to item Cite

Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin.

Journal Article Sci Signal · August 9, 2011 Phosphorylation of G protein-coupled receptors (GPCRs, which are also known as seven-transmembrane spanning receptors) by GPCR kinases (GRKs) plays essential roles in the regulation of receptor function by promoting interactions of the receptors with β-arr ... Full text Link to item Cite

Beta2-adrenergic receptor lysosomal trafficking is regulated by ubiquitination of lysyl residues in two distinct receptor domains.

Journal Article J Biol Chem · April 8, 2011 Featured Publication Agonist stimulation of the β2-adrenergic receptors (β2ARs) leads to their ubiquitination and lysosomal degradation. Inhibition of lysosomal proteases results in the stabilization and retention of internalized full-length β2ARs in the lysosomes, whereas inh ... Full text Link to item Cite

β-arrestin-biased signaling by the β-adrenergic receptors.

Journal Article Curr Top Membr · 2011 Featured Publication Full text Link to item Cite

Visualizing G protein-coupled receptor signalsomes using confocal immunofluorescence microscopy.

Journal Article Methods Mol Biol · 2011 The heptahelical G protein-coupled receptors (GPCRs) receive and transmit a wide range of extracellular stimuli and induce a wide array of cellular responses by activating signaling kinases. It has become increasingly evident that the agonist-stimulated GP ... Full text Link to item Cite

Arresting a transient receptor potential (TRP) channel: beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4.

Journal Article J Biol Chem · September 24, 2010 β-Arrestins, originally discovered to desensitize activated G protein-coupled receptors, (aka seven-transmembrane receptors, 7TMRs) also mediate 7TMR internalization and G protein-independent signaling via these receptors. More recently, several regulatory ... Full text Link to item Cite

The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization.

Journal Article EMBO J · June 17, 2009 Featured Publication Agonist-induced ubiquitination of the beta(2) adrenergic receptor (beta(2)AR) functions as an important post-translational modification to sort internalized receptors to the lysosomes for degradation. We now show that this ubiquitination is reversed by two ... Full text Link to item Cite

Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2.

Journal Article Proc Natl Acad Sci U S A · April 21, 2009 Featured Publication Beta-arrestins are multifunctional adaptors that mediate the desensitization, internalization, and some signaling functions of seven-transmembrane receptors (7TMRs). Agonist-stimulated ubiquitination of beta-arrestin2 mediated by the E3 ubiquitin ligase Md ... Full text Link to item Cite

Reciprocal regulation of the platelet-derived growth factor receptor-beta and G protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis.

Journal Article Mol Pharmacol · March 2009 Signaling by the platelet-derived growth factor receptor-beta (PDGFRbeta) is diminished when the PDGFRbeta is phosphorylated on seryl residues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbeta remain obscure ... Full text Link to item Cite

Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor.

Journal Article J Biol Chem · August 8, 2008 Featured Publication Agonist-stimulated beta(2)-adrenergic receptor (beta(2)AR) ubiquitination is a major factor that governs both lysosomal trafficking and degradation of internalized receptors, but the identity of the E3 ubiquitin ligase regulating this process was unknown. ... Full text Link to item Cite

Distinct conformational changes in beta-arrestin report biased agonism at seven-transmembrane receptors.

Journal Article Proc Natl Acad Sci U S A · July 22, 2008 Beta-arrestins critically regulate G protein-coupled receptors (GPCRs), also known as seven-transmembrane receptors (7TMRs), both by inhibiting classical G protein signaling and by initiating distinct beta-arrestin-mediated signaling. The recent discovery ... Full text Link to item Cite

beta-arrestin-biased agonism at the beta2-adrenergic receptor.

Journal Article J Biol Chem · February 29, 2008 Classically, the beta 2-adrenergic receptor (beta 2AR) and other members of the seven-transmembrane receptor (7TMR) superfamily activate G protein-dependent signaling pathways in response to ligand stimulus. It has recently been discovered, however, that a ... Full text Link to item Cite

A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.

Journal Article Proc Natl Acad Sci U S A · October 16, 2007 For many years, beta-adrenergic receptor antagonists (beta-blockers or betaAR antagonists) have provided significant morbidity and mortality benefits in patients who have sustained acute myocardial infarction. More recently, beta-adrenergic receptor antago ... Full text Link to item Cite

Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation.

Journal Article J Biol Chem · October 5, 2007 Featured Publication Beta-arrestin2 and its ubiquitination play crucial roles in both internalization and signaling of seven-transmembrane receptors (7TMRs). To understand the connection between ubiquitination and the endocytic and signaling functions of beta-arrestin, we gene ... Full text Link to item Cite

Functional specialization of beta-arrestin interactions revealed by proteomic analysis.

Journal Article Proc Natl Acad Sci U S A · July 17, 2007 Beta-arrestins are cytosolic proteins that form complexes with seven-transmembrane receptors after agonist stimulation and phosphorylation by the G protein-coupled receptor kinases. They play an essential role in receptor desensitization and endocytosis, a ... Full text Link to item Cite

Seven-transmembrane receptors and ubiquitination.

Journal Article Circ Res · April 27, 2007 Featured Publication Regulation of protein function by posttranslational modification plays an important role in many biological pathways. The most well known among such modifications is protein phosphorylation performed by highly specific protein kinases. In the past decade, ... Full text Link to item Cite

Beta-arrestin and Mdm2 mediate IGF-1 receptor-stimulated ERK activation and cell cycle progression.

Journal Article J Biol Chem · April 13, 2007 Featured Publication Beta-arrestin1, which regulates many aspects of seven transmembrane receptor (7TMR) biology, has also been shown to serve as an adaptor, which brings Mdm2, an E3 ubiquitin ligase to the insulin-like growth factor-1 receptor (IGF-1R), leading to its proteas ... Full text Link to item Cite

Beta-arrestins and cell signaling.

Journal Article Annu Rev Physiol · 2007 Featured Publication Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows ... Full text Link to item Cite

Trafficking of G protein-coupled receptors.

Journal Article Circ Res · September 15, 2006 G protein-coupled receptors (GPCRs) play an integral role in the signal transduction of an enormous array of biological phenomena, thereby serving to modulate at a molecular level almost all components of human biology. This role is nowhere more evident th ... Full text Open Access Link to item Cite

beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor.

Journal Article J Biol Chem · January 13, 2006 Featured Publication Physiological effects of beta adrenergic receptor (beta2AR) stimulation have been classically shown to result from G(s)-dependent adenylyl cyclase activation. Here we demonstrate a novel signaling mechanism wherein beta-arrestins mediate beta2AR signaling ... Full text Link to item Cite

Receptor regulation: beta-arrestin moves up a notch.

Journal Article Nat Cell Biol · December 2005 Featured Publication Full text Link to item Cite

Angiotensin II-stimulated signaling through G proteins and beta-arrestin.

Journal Article Sci STKE · November 22, 2005 Featured Publication Beta-arrestin, originally identified as a protein that inhibits heterotrimeric guanine nucleotide-binding protein (G protein) coupling to cognate seven-transmembrane receptors [(7TMRs), also known as G protein-coupled receptors (GPCRs)], is currently being ... Full text Link to item Cite

Seven-transmembrane receptor signaling through beta-arrestin.

Journal Article Sci STKE · November 1, 2005 Featured Publication Cell surface receptors are important communicators of external stimuli to the cell interior where they lead to initiation of various signaling pathways and cellular responses. The largest receptor family is the seven-transmembrane receptor (7TMR) family, w ... Full text Link to item Cite

{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase.

Journal Article J Biol Chem · July 1, 2005 The insulin-like growth factor-1 receptor (IGF-1R) plays important roles in physiological growth and aging as well as promoting several crucial functions in cancer cells. However, the molecular mechanisms involved in expression and down-regulation of IGF-1 ... Full text Link to item Cite

Transduction of receptor signals by beta-arrestins.

Journal Article Science · April 22, 2005 Featured Publication The transmission of extracellular signals to the interior of the cell is a function of plasma membrane receptors, of which the seven transmembrane receptor family is by far the largest and most versatile. Classically, these receptors stimulate heterotrimer ... Full text Link to item Cite

Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes.

Journal Article J Biol Chem · April 15, 2005 Featured Publication Angiotensin II type 1a (AT1a), vasopressin V2, and neurokinin 1 (NK1) receptors are seven-transmembrane receptors (7TMRs) that bind and co-internalize with the multifunctional adaptor protein, beta-arrestin. These receptors also lead to robust and persiste ... Full text Link to item Cite

Activation dependent conformational changes in beta-arrestin 2

Conference BIOPHYSICAL JOURNAL · January 1, 2005 Link to item Cite

Constitutive protease-activated receptor-2-mediated migration of MDA MB-231 breast cancer cells requires both beta-arrestin-1 and -2.

Journal Article J Biol Chem · December 31, 2004 Featured Publication Protease-activated receptor-2 (PAR-2) is activated by trypsin-like serine proteases and can promote cell migration through an ERK1/2-dependent pathway, involving formation of a scaffolding complex at the leading edge of the cell. Previous studies also show ... Full text Link to item Cite

Activation-dependent conformational changes in {beta}-arrestin 2.

Journal Article J Biol Chem · December 31, 2004 Beta-arrestins are multifunctional adaptor proteins, which mediate desensitization, endocytosis, and alternate signaling pathways of seven membrane-spanning receptors (7MSRs). Crystal structures of the basal inactive state of visual arrestin (arrestin 1) a ... Full text Link to item Cite

Resonating to the music of ubiquitination.

Journal Article Nat Methods · December 2004 Featured Publication Full text Link to item Cite

beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1.

Journal Article Mol Cell Biol · October 2004 beta-arrestin-1 is an adaptor protein that mediates agonist-dependent internalization and desensitization of G-protein-coupled receptors (GPCRs) and also participates in the process of heterologous desensitization between receptor tyrosine kinases and GPCR ... Full text Open Access Link to item Cite

Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor.

Journal Article J Biol Chem · August 20, 2004 The seven-membrane-spanning angiotensin II type 1A receptor activates the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2) by distinct pathways dependent on either G protein (likely G(q)/G(11)) or beta-arrestin2. He ... Full text Link to item Cite

Regulation of V2 vasopressin receptor degradation by agonist-promoted ubiquitination.

Journal Article J Biol Chem · November 14, 2003 Featured Publication The seven-transmembrane-spanning vasopressin V2 receptor (V2R) is a Gs-coupled receptor that is rapidly phosphorylated and internalized following stimulation with the agonist, arginine-vasopressin. Herein, we show that the V2R is ubiquitinated following ag ... Full text Link to item Cite

Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling.

Journal Article Biochem J · November 1, 2003 Featured Publication Beta-arrestins are cytosolic proteins that bind to activated and phosphorylated G-protein-coupled receptors [7MSRs (seven-membrane-spanning receptors)] and uncouple them from G-protein-mediated second messenger signalling pathways. The binding of beta-arre ... Full text Link to item Cite

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

Journal Article Proc Natl Acad Sci U S A · September 16, 2003 Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recr ... Full text Open Access Link to item Cite

Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination.

Journal Article J Biol Chem · April 18, 2003 Featured Publication Agonist-dependent internalization of G protein-coupled receptors via clathrin-coated pits is dependent on the adaptor protein beta-arrestin, which interacts with elements of the endocytic machinery such as AP2 and clathrin. For the beta(2)-adrenergic recep ... Full text Link to item Cite

Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors.

Journal Article Biochemistry · August 27, 2002 Beta-arrestins mediate agonist-dependent desensitization and internalization of G protein-coupled receptors. Previously, we have shown that phosphorylation of beta-arrestin1 by ERKs at Ser-412 regulates its association with clathrin and its function in pro ... Full text Link to item Cite

Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin.

Journal Article Science · November 9, 2001 Featured Publication Although trafficking and degradation of several membrane proteins are regulated by ubiquitination catalyzed by E3 ubiquitin ligases, there has been little evidence connecting ubiquitination with regulation of mammalian G protein (heterotrimeric guanine nuc ... Full text Link to item Cite

Reconstitution of mitochondrial processing peptidase from the core proteins (subunits I and II) of bovine heart mitochondrial cytochrome bc(1) complex.

Journal Article J Biol Chem · March 2, 2001 Mature core I and core II proteins of the bovine heart mitochondrial cytochrome bc(1) complex were individually overexpressed in Escherichia coli as soluble proteins using the expression vector pET-I and pET-II, respectively. Purified recombinant core I an ... Full text Link to item Cite

Subunit IV of cytochrome bc1 complex from Rhodobacter sphaeroides. Localization of regions essential for interaction with the three-subunit core complex.

Journal Article J Biol Chem · May 19, 2000 Recombinant subunit IV mutants which identify the regions essential for restoration of bc(1) activity to the three-subunit core complex of Rhodobacter sphaeroides were generated and characterized. Four C-terminal truncated mutants: IV(1-109), IV(1-85), IV( ... Full text Link to item Cite

Structural basis of multifunctional bovine mitochondrial cytochrome bc1 complex.

Journal Article J Bioenerg Biomembr · June 1999 The mitochondrial cytochrome bc1 complex is a multifunctional membrane protein complex. It catalyzes electron transfer, proton translocation, peptide processing, and superoxide generation. Crystal structure data at 2.9 A resolution not only establishes the ... Full text Link to item Cite

The role of the supernumerary subunit of Rhodobacter sphaeroides cytochrome bc1 complex.

Journal Article J Bioenerg Biomembr · June 1999 The smallest molecular weight subunit (subunit IV), which contains no redox prosthetic group, is the only supernumerary subunit in the four-subunit Rhodobacter sphaeroides bc1 complex. This subunit is involved in Q binding and the structural integrity of t ... Full text Link to item Cite

Identification of quinone-binding and heme-ligating residues of the smallest membrane-anchoring subunit (QPs3) of bovine heart mitochondrial succinate:ubiquinone reductase.

Journal Article J Biol Chem · March 26, 1999 The smallest membrane-anchoring subunit (QPs3) of bovine heart succinate:ubiquinone reductase was overexpressed in Escherichia coli JM109 as a glutathione S-transferase fusion protein using the expression vector pGEX2T/QPs3. The yield of soluble active rec ... Full text Link to item Cite

The smallest membrane anchoring subunit (QPs3) of bovine heart mitochondrial succinate-ubiquinone reductase. Cloning, sequencing, topology, and Q-binding domain.

Journal Article J Biol Chem · July 11, 1997 The cDNA encoding the smallest membrane-anchoring subunit (QPs3) of bovine heart mitochondrial succinate-ubiquinone reductase was cloned and sequenced. This cDNA is 1330 base pairs long with an open reading frame of 474 base pairs that encodes the 103 amin ... Full text Link to item Cite

Cloning and sequencing of QPS3 of mitochondrial succinate -Q reductase

Journal Article FASEB Journal · December 1, 1996 Bovine heart mitochondnal succinate-ubiquinone reductase (SQR),which catalyses electron transfer from succinate to ubiquinone, is composed of a soluble succinate dehydrogenase (SDK) and a membrane anchoring protein fraction (QPs). QPs forms Q-binding site( ... Cite

Identification of amino acid residues involved in structural and ubiquinone-binding functions of subunit IV of the cytochrome bc1 complex from Rhodobacter sphaeroides.

Journal Article J Biol Chem · May 12, 1995 Previous studies established that subunit IV of the cytochrome bc1 complex from Rhodobacter sphaeroides is involved in structural and ubiquinone-binding functions of the complex. To identify regions or amino acid residues responsible for these functions, d ... Full text Link to item Cite