Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of Cyclic Nucleotide Phosphodiesterases

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 than in cardiovascular biology, where GPCRs regulate such core measures of cardiovascular function as heart rate, contractility, and vascular tone. GPCR/ligand interaction initiates signal transduction cascades, and requires the presence of the receptor at the plasma membrane. Plasma membrane localization is in turn a function of the delivery of a receptor to and removal from the cell surface, a concept defined most broadly as receptor trafficking. This review illuminates our current view of GPCR trafficking, particularly within the cardiovascular system, as well as highlights the recent and provocative finding that components of the GPCR trafficking machinery can facilitate GPCR signaling independent of G protein activation.

[1]  J. W. Wells,et al.  Oligomeric potential of the M2 muscarinic cholinergic receptor , 2004, Journal of neurochemistry.

[2]  P. Fishman,et al.  Resistance of the human beta1-adrenergic receptor to agonist-induced ubiquitination: a mechanism for impaired receptor degradation. , 2004, The Journal of biological chemistry.

[3]  T. Magnuson,et al.  An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. , 2005, Molecular biology of the cell.

[4]  S. Shenolikar,et al.  The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange , 1998, Nature.

[5]  R. Lefkowitz,et al.  GIT Proteins, A Novel Family of Phosphatidylinositol 3,4,5-Trisphosphate-stimulated GTPase-activating Proteins for ARF6* , 2000, The Journal of Biological Chemistry.

[6]  L. Meinel,et al.  Intracellular trafficking of angiotensin II and its AT1 and AT2 receptors: evidence for selective sorting of receptor and ligand. , 1997, Molecular endocrinology.

[7]  M. Caron,et al.  Rab5 Association with the Angiotensin II Type 1A Receptor Promotes Rab5 GTP Binding and Vesicular Fusion* , 2002, The Journal of Biological Chemistry.

[8]  R. Lefkowitz,et al.  When 7 transmembrane receptors are not G protein-coupled receptors. , 2005, Journal of Clinical Investigation.

[9]  Ari Helenius,et al.  Quality control in the endoplasmic reticulum , 2003, Nature Reviews Molecular Cell Biology.

[10]  M. von Zastrow,et al.  Role of Mammalian Vacuolar Protein-sorting Proteins in Endocytic Trafficking of a Non-ubiquitinated G Protein-coupled Receptor to Lysosomes* , 2004, Journal of Biological Chemistry.

[11]  Liaoyuan A. Hu,et al.  β1-Adrenergic Receptor Association with PSD-95 , 2000, The Journal of Biological Chemistry.

[12]  L. Hunyady,et al.  Intracellular trafficking of hormone receptors , 2004, Trends in Endocrinology & Metabolism.

[13]  J. Benovic,et al.  β-Arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptor , 1996, Nature.

[14]  M. Caron,et al.  Dynamin and β-Arrestin Reveal Distinct Mechanisms for G Protein-coupled Receptor Internalization* , 1996, The Journal of Biological Chemistry.

[15]  T. Kohout,et al.  Regulation of Receptor Fate by Ubiquitination of Activated β2-Adrenergic Receptor and β-Arrestin , 2001, Science.

[16]  J. Thorner,et al.  Model systems for the study of seven-transmembrane-segment receptors. , 1991, Annual review of biochemistry.

[17]  M. Caron,et al.  beta-Arrestin: a protein that regulates beta-adrenergic receptor function. , 1990, Science.

[18]  M. Caron,et al.  Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. , 2000, The Journal of biological chemistry.

[19]  M. Donowitz,et al.  Na+/H+ exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling , 2002, Nature.

[20]  A. Bretscher,et al.  A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor , 1999, Nature.

[21]  R. Lefkowitz,et al.  The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. , 2002, Journal of cell science.

[22]  H. Dadi,et al.  Muscarinic cholinergic receptor of rat brain , 1984 .

[23]  B. Kobilka,et al.  The PDZ Binding Motif of the β1 Adrenergic Receptor Modulates Receptor Trafficking and Signaling in Cardiac Myocytes* , 2002, The Journal of Biological Chemistry.

[24]  P. H. Anborgh,et al.  beta 2-adrenergic receptor internalization, endosomal sorting, and plasma membrane recycling are regulated by rab GTPases. , 2000, The Journal of biological chemistry.

[25]  B. Kobilka,et al.  Caveolar Localization Dictates Physiologic Signaling of β2-Adrenoceptors in Neonatal Cardiac Myocytes* , 2002, The Journal of Biological Chemistry.

[26]  M. Caron,et al.  Role of β-Arrestin in Mediating Agonist-Promoted G Protein-Coupled Receptor Internalization , 1996, Science.

[27]  Liaoyuan A. Hu,et al.  Binding of the β2 Adrenergic Receptor toN-Ethylmaleimide-sensitive Factor Regulates Receptor Recycling* , 2001, The Journal of Biological Chemistry.

[28]  Michel Bouvier,et al.  Pharmacological chaperones: potential treatment for conformational diseases , 2004, Trends in Endocrinology & Metabolism.

[29]  J. Benovic,et al.  Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. , 1996, Nature.

[30]  M. Freissmuth,et al.  The Ubiquitin-Specific Protease Usp4 Regulates the Cell Surface Level of the A2a Receptor , 2006, Molecular Pharmacology.

[31]  R. Lefkowitz,et al.  beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Hancock,et al.  Caveolin Interacts with the Angiotensin II Type 1 Receptor during Exocytic Transport but Not at the Plasma Membrane* , 2003, Journal of Biological Chemistry.

[33]  G. Dorn,et al.  Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Wess,et al.  Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. , 1998, Biochemistry.

[35]  R. Lefkowitz,et al.  Trafficking Patterns of β-Arrestin and G Protein-coupled Receptors Determined by the Kinetics of β-Arrestin Deubiquitination* , 2003, The Journal of Biological Chemistry.

[36]  R. Lefkowitz,et al.  Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Kurten,et al.  Enhanced Degradation of EGF Receptors by a Sorting Nexin, SNX1 , 1996, Science.

[38]  Alexander Varshavsky,et al.  The ubiquitin system. , 1998, Annual review of biochemistry.

[39]  M. Caron,et al.  Phosphoinositide 3-kinase regulates β2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/β-arrestin complex , 2002, The Journal of cell biology.

[40]  Susan R. George,et al.  G-Protein-coupled receptor oligomerization and its potential for drug discovery , 2002, Nature Reviews Drug Discovery.

[41]  M. Caron,et al.  The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Caron,et al.  A small region of the beta-adrenergic receptor is selectively involved in its rapid regulation. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Antonio S. Tutor,et al.  Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease. , 2006, Cardiovascular research.

[44]  S. Ferguson,et al.  Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. , 2001, Pharmacological reviews.

[45]  Krzysztof Palczewski,et al.  Oligomerization of G protein-coupled receptors: past, present, and future. , 2004, Biochemistry.

[46]  R. Lefkowitz,et al.  G protein-coupled receptor kinases. , 1998, Annual review of biochemistry.

[47]  J. Backer.  Substrate specificity: PI(3)Kγ has it both ways , 2005, Nature Cell Biology.

[48]  C. Créminon,et al.  Role of the carboxyl‐terminal region, di‐leucine motif and cysteine residues in signalling and internalization of vasopressin V1a receptor , 1999, FEBS letters.

[49]  R. Lefkowitz,et al.  beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis. , 2001, The Journal of biological chemistry.

[50]  J. Benovic,et al.  Agonist-promoted Ubiquitination of the G Protein-coupled Receptor CXCR4 Mediates Lysosomal Sorting* , 2001, The Journal of Biological Chemistry.

[51]  R. Wojcikiewicz.  Regulated ubiquitination of proteins in GPCR-initiated signaling pathways. , 2004, Trends in pharmacological sciences.

[52]  Michel Bouvier,et al.  A Peptide Derived from a β2-Adrenergic Receptor Transmembrane Domain Inhibits Both Receptor Dimerization and Activation* , 1996, The Journal of Biological Chemistry.

[53]  T. Kohout,et al.  beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  P. Insel,et al.  Caveolae and Lipid Rafts: G Protein‐Coupled Receptor Signaling Microdomains in Cardiac Myocytes , 2005, Annals of the New York Academy of Sciences.

[55]  Alan Wise,et al.  Target validation of G-protein coupled receptors. , 2002, Drug discovery today.

[56]  Jie Zhang,et al.  The β2-adrenergic receptor/βarrestin complex recruits the clathrin adaptor AP-2 during endocytosis , 1999 .

[57]  M. Welsh,et al.  A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[58]  I. Braakman,et al.  Quality control in the endoplasmic reticulum protein factory , 2003, Nature.

[59]  J. Benovic,et al.  Role of Arrestins in Endocytosis and Signaling of α2-Adrenergic Receptor Subtypes* , 1999, Journal of Biological Chemistry.

[60]  J. B. Higgins,et al.  Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. , 1992, Science.

[61]  R. Lefkowitz,et al.  Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors. , 2002, Biochemistry.

[62]  L. Liu-Chen.  Agonist-induced regulation and trafficking of kappa opioid receptors. , 2004, Life sciences.

[63]  C. Aoki,et al.  Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family. , 1992, The Journal of biological chemistry.

[64]  R. Lefkowitz,et al.  Angiotensin II–Stimulated Signaling Through G Proteins and β-Arrestin , 2005, Science's STKE.

[65]  M. Gonzalez-Gaitan,et al.  Endocytosis and Signaling A Relationship under Development , 2003, Cell.

[66]  B. Kobilka,et al.  Antagonist-dependent and -independent steps in the mechanism of adrenergic receptor internalization. , 1994, The Journal of biological chemistry.

[67]  R. Lefkowitz,et al.  Identification of the cardiac beta-adrenergic receptor protein: solubilization and purification by affinity chromatography. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[68]  C. Ross,et al.  β1-Adrenergic Receptor Association with the Synaptic Scaffolding Protein Membrane-associated Guanylate Kinase Inverted-2 (MAGI-2) , 2001, The Journal of Biological Chemistry.

[69]  Patricia H Reggio,et al.  Lipids, lipid rafts and caveolae: their importance for GPCR signaling and their centrality to the endocannabinoid system. , 2005, Life sciences.

[70]  M. Caron,et al.  A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration. , 1994, The Journal of biological chemistry.

[71]  S. Ferguson,et al.  Regulation of G protein-coupled receptor endocytosis and trafficking by Rab GTPases. , 2003, Life sciences.

[72]  M. Caron,et al.  Endocytosis of G protein-coupled receptors: roles of G protein-coupled receptor kinases and ß-arrestin proteins , 2002, Progress in Neurobiology.

[73]  Robert J. Lefkowitz,et al.  Classical and new roles of β-arrestins in the regulation of G-PROTEIN-COUPLED receptors , 2001, Nature Reviews Neuroscience.

[74]  H. Akil,et al.  Inhibition of cell surface expression by mutant receptors demonstrates that D2 dopamine receptors exist as oligomers in the cell. , 2000, Molecular pharmacology.

[75]  Michel Bouvier,et al.  Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation. , 2005, Trends in pharmacological sciences.

[76]  R. Lefkowitz,et al.  Receptor-specific Ubiquitination of β-Arrestin Directs Assembly and Targeting of Seven-transmembrane Receptor Signalosomes* , 2005, Journal of Biological Chemistry.

[77]  Olivier Lichtarge,et al.  β-Arrestin-dependent, G Protein-independent ERK1/2 Activation by the β2 Adrenergic Receptor* , 2006, Journal of Biological Chemistry.

[78]  R. Lefkowitz,et al.  Desensitization, internalization, and signaling functions of β-arrestins demonstrated by RNA interference , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[79]  J. Trejo,et al.  A Tyrosine-based Sorting Signal Regulates Intracellular Trafficking of Protease-activated Receptor-1 , 2004, Journal of Biological Chemistry.

[80]  B. O'dowd,et al.  Homo- and hetero-oligomerization of G protein-coupled receptors. , 2003, Life sciences.

[81]  A. Burlingame,et al.  Mass spectrometric analysis of agonist effects on posttranslational modifications of the beta-2 adrenoceptor in mammalian cells. , 2005, Biochemistry.

[82]  J. Benovic.  Purification and characterization of beta-adrenergic receptor kinase. , 1987, Methods in enzymology.

[83]  R. Lefkowitz,et al.  Feedback Regulation of β-Arrestin1 Function by Extracellular Signal-regulated Kinases* , 1999, The Journal of Biological Chemistry.

[84]  G. Cottrell,et al.  c-Cbl Mediates Ubiquitination, Degradation, and Down-regulation of Human Protease-activated Receptor 2* , 2005, Journal of Biological Chemistry.

[85]  Linda Hicke,et al.  Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. , 2003, Annual review of cell and developmental biology.

[86]  R. Lefkowitz,et al.  Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. , 1999, The Journal of biological chemistry.

[87]  C. Hague,et al.  Cell surface expression of alpha1D-adrenergic receptors is controlled by heterodimerization with alpha1B-adrenergic receptors. , 2004, The Journal of biological chemistry.

[88]  M. Caron,et al.  Association of β-Arrestin with G Protein-coupled Receptors during Clathrin-mediated Endocytosis Dictates the Profile of Receptor Resensitization* , 1999, The Journal of Biological Chemistry.

[89]  R. Lefkowitz,et al.  Distinct β-Arrestin- and G Protein-dependent Pathways for Parathyroid Hormone Receptor-stimulated ERK1/2 Activation* , 2006, Journal of Biological Chemistry.

[90]  Michel Bouvier,et al.  Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. , 2002, Annual review of pharmacology and toxicology.

[91]  N. Bunnett,et al.  Regulatory mechanisms that modulate signalling by G-protein-coupled receptors. , 1997, The Biochemical journal.

[92]  C. Ross,et al.  beta 1-adrenergic receptor association with the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation of receptor internalization by MAGI-2 and PSD-95. , 2001, The Journal of biological chemistry.

[93]  Soma Das,et al.  Mutations in the V2 vasopressin receptor gene are associated with X–linked nephrogenic diabetes insipidus , 1992, Nature Genetics.

[94]  J. Benovic,et al.  Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5. , 1994, The Journal of biological chemistry.

[95]  S. Shenolikar,et al.  The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange. , 1998, Nature.

[96]  D. Chuang,et al.  Evidence for internalization of the recognition site of beta-adrenergic receptors during receptor subsensitivity induced by (-)-isoproterenol. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[97]  S. Angers,et al.  Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. , 2000, The Journal of clinical investigation.

[98]  R. Lefkowitz,et al.  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* , 2004, Journal of Biological Chemistry.

[99]  S. Mundell,et al.  Arrestin isoforms dictate differential kinetics of A2B adenosine receptor trafficking. , 2000, Biochemistry.

[100]  G. Entine,et al.  Lateral Diffusion of Visual Pigment in Photoreceptor Disk Membranes , 1974, Science.

[101]  R. Mullins,et al.  β-Arrestin–Dependent Endocytosis of Proteinase-Activated Receptor 2 Is Required for Intracellular Targeting of Activated Erk1/2 , 2000, The Journal of cell biology.

[102]  S. Bonhoeffer,et al.  HIV-1 Evolution and Disease Progression , 1996, Science.

[103]  Jean-François Mercier,et al.  Homodimerization of the β2-Adrenergic Receptor as a Prerequisite for Cell Surface Targeting* , 2004, Journal of Biological Chemistry.

[104]  N. W. Downer,et al.  Transient dichroism in photoreceptor membranes indicates that stable oligomers of rhodopsin do not form during excitation. , 1985, Biophysical journal.

[105]  M. von Zastrow,et al.  Modulation of Postendocytic Sorting of G Protein-Coupled Receptors , 2002, Science.

[106]  Martin J. Lohse,et al.  Mutations of Tyr326 in the β2-adrenoceptor disrupt multiple receptor functions , 1996 .

[107]  M. Lohse,et al.  A dileucine motif in the C terminus of the beta2-adrenergic receptor is involved in receptor internalization. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[108]  M. Cheetham,et al.  The Chaperone Environment at the Cytoplasmic Face of the Endoplasmic Reticulum Can Modulate Rhodopsin Processing and Inclusion Formation* , 2003, Journal of Biological Chemistry.

[109]  R. Lefkowitz,et al.  beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors. , 2000, The Journal of biological chemistry.

[110]  Robert J. Lefkowitz,et al.  Transduction of Receptor Signals by ß-Arrestins , 2005, Science.

[111]  R. Lefkowitz,et al.  Multifaceted roles of β-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling , 2003 .

[112]  R. Lefkowitz,et al.  Protein Kinase A and G Protein-coupled Receptor Kinase Phosphorylation Mediates β-1 Adrenergic Receptor Endocytosis through Different Pathways* , 2003, Journal of Biological Chemistry.

[113]  Bianca Habermann,et al.  Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis , 2005, Nature.

[114]  C. Hague,et al.  Cell Surface Expression of α1D-Adrenergic Receptors Is Controlled by Heterodimerization with α1B-Adrenergic Receptors* , 2004, Journal of Biological Chemistry.

[115]  M. Mortrud,et al.  The G protein-coupled receptor repertoires of human and mouse , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[116]  R. Lefkowitz,et al.  Identification, purification, and characterization of GRK5, a member of the family of G protein-coupled receptor kinases. , 1994, The Journal of biological chemistry.

[117]  M. Parenti,et al.  G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there? , 2004, Journal of molecular endocrinology.

[118]  R. Lefkowitz,et al.  Identification of NSF as a β-Arrestin1-binding Protein , 1999, The Journal of Biological Chemistry.

[119]  S. V. Prasad,et al.  Protein kinase activity of phosphoinositide 3-kinase regulates β-adrenergic receptor endocytosis , 2005, Nature Cell Biology.

[120]  Liaoyuan A. Hu,et al.  Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[121]  P. Insel,et al.  Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae. , 2005, Biochemical Society transactions.

[122]  L. Abuin,et al.  The Adaptor Complex 2 Directly Interacts with the α1b-Adrenergic Receptor and Plays a Role in Receptor Endocytosis* , 2003, Journal of Biological Chemistry.

[123]  R. Lefkowitz,et al.  Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. , 2003, The Journal of biological chemistry.

[124]  S. Ferguson,et al.  Regulation of Angiotensin II Type 1A Receptor Intracellular Retention, Degradation, and Recycling by Rab5, Rab7, and Rab11 GTPases* , 2004, Journal of Biological Chemistry.

[125]  B. Mouillac,et al.  Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. , 2003, Molecular endocrinology.

[126]  M. Caron,et al.  Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. , 1999, Science.

[127]  L. Liu-Chen.  Agonist-induced regulation and trafficking of κ opioid receptors , 2004 .

[128]  D. Richter,et al.  The 5-Hydroxytryptamine(1A) Receptor Is Stably Palmitoylated, and Acylation Is Critical for Communication of Receptor with Gi Protein* , 2004, Journal of Biological Chemistry.

[129]  L. Devi,et al.  Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[130]  R. Stoffel,et al.  Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family. , 1994, The Journal of biological chemistry.

[131]  B. Wiesner,et al.  A dileucine sequence and an upstream glutamate residue in the intracellular carboxyl terminus of the vasopressin V2 receptor are essential for cell surface transport in COS.M6 cells. , 1998, Molecular pharmacology.

[132]  Frédérique Verdier,et al.  Both proteasomes and lysosomes degrade the activated erythropoietin receptor. , 2005, Blood.

[133]  C. Hague,et al.  Heterodimerization with β2-Adrenergic Receptors Promotes Surface Expression and Functional Activity of α1D-Adrenergic Receptors , 2005, Journal of Pharmacology and Experimental Therapeutics.

[134]  J. Benovic,et al.  The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. , 2003, Developmental cell.

[135]  Olivier Lichtarge,et al.  beta-arrestin-dependent, G protein-independent ERK1/2 activation by the beta2 adrenergic receptor. , 2006, The Journal of biological chemistry.

[136]  R. Lefkowitz,et al.  Regulation of V2 Vasopressin Receptor Degradation by Agonist-promoted Ubiquitination* , 2003, Journal of Biological Chemistry.

[137]  R. Lefkowitz,et al.  Identification of the G Protein-coupled Receptor Kinase Phosphorylation Sites in the Human β2-Adrenergic Receptor* , 1996, The Journal of Biological Chemistry.

[138]  K. Ressler,et al.  Olfactory receptor surface expression is driven by association with the beta2-adrenergic receptor. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[139]  C. Haft,et al.  Down-regulation of protease-activated receptor-1 is regulated by sorting nexin 1. , 2002, Molecular biology of the cell.

[140]  M. Caron,et al.  Agonist-dependent Recruitment of Phosphoinositide 3-Kinase to the Membrane by β-Adrenergic Receptor Kinase 1 , 2001, The Journal of Biological Chemistry.

[141]  Christopher M. Tan,et al.  Membrane trafficking of G protein-coupled receptors. , 2004, Annual review of pharmacology and toxicology.

[142]  C. Hague,et al.  Heterodimerization with beta2-adrenergic receptors promotes surface expression and functional activity of alpha1D-adrenergic receptors. , 2005, The Journal of pharmacology and experimental therapeutics.