Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 294 (5545): 1307-1313

Copyright © 2001 by the American Association for the Advancement of Science

Regulation of Receptor Fate by Ubiquitination of Activated beta 2-Adrenergic Receptor and beta -Arrestin

Sudha K. Shenoy, Patricia H. McDonald, Trudy A. Kohout, Robert J. Lefkowitz*

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 nucleotide-binding protein)-coupled receptor (GPCR) function. Agonist stimulation of endogenous or transfected beta 2-adrenergic receptors (beta 2ARs) led to rapid ubiquitination of both the receptors and the receptor regulatory protein, beta -arrestin. Moreover, proteasome inhibitors reduced receptor internalization and degradation, thus implicating a role for the ubiquitination machinery in the trafficking of the beta 2AR. Receptor ubiquitination required beta -arrestin, which bound to the E3 ubiquitin ligase Mdm2. Abrogation of beta -arrestin ubiquitination, either by expression in Mdm2-null cells or by dominant-negative forms of Mdm2 lacking E3 ligase activity, inhibited receptor internalization with marginal effects on receptor degradation. However, a beta 2AR mutant lacking lysine residues, which was not ubiquitinated, was internalized normally but was degraded ineffectively. These findings delineate an adapter role of beta -arrestin in mediating the ubiquitination of the beta 2AR and indicate that ubiquitination of the receptor and of beta -arrestin have distinct and obligatory roles in the trafficking and degradation of this prototypic GPCR.

Howard Hughes Medical Institute and Departments of Medicine, Cardiology and Biochemistry, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.
*   To whom correspondence should be addressed: E-mail: lefko001{at}

{alpha}-Arrestins - new players in Notch and GPCR signaling pathways in mammals.
L. Puca and C. Brou (2014)
J. Cell Sci. 127, 1359-1367
   Abstract »    Full Text »    PDF »
Ubiquitin-Dependent Sorting in Endocytosis.
R. C. Piper, I. Dikic, and G. L. Lukacs (2014)
Cold Spring Harb Perspect Biol 6, a016808
   Abstract »    Full Text »    PDF »
Endocytosis and Cancer.
I. Mellman and Y. Yarden (2013)
Cold Spring Harb Perspect Biol 5, a016949
   Abstract »    Full Text »    PDF »
{alpha}-arrestin 1 (ARRDC1) and {beta}-arrestins cooperate to mediate Notch degradation in mammals.
L. Puca, P. Chastagner, V. Meas-Yedid, A. Israel, and C. Brou (2013)
J. Cell Sci. 126, 4457-4468
   Abstract »    Full Text »    PDF »
{beta}-Arrestins 1 and 2 are critical regulators of inflammation.
H. Fan (2013)
Innate Immunity
   Abstract »    Full Text »    PDF »
The fission yeast {beta}-arrestin-like protein Any1 is involved in TSC-Rheb signaling and the regulation of amino acid transporters.
Y. Nakase, M. Nakase, J. Kashiwazaki, T. Murai, Y. Otsubo, I. Mabuchi, M. Yamamoto, K. Takegawa, and T. Matsumoto (2013)
J. Cell Sci. 126, 3972-3981
   Abstract »    Full Text »    PDF »
Brain-specific Angiogenesis Inhibitor-1 Signaling, Regulation, and Enrichment in the Postsynaptic Density.
J. R. Stephenson, K. J. Paavola, S. A. Schaefer, B. Kaur, E. G. Van Meir, and R. A. Hall (2013)
J. Biol. Chem. 288, 22248-22256
   Abstract »    Full Text »    PDF »
Heterozygous LmnadelK32 mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity.
M.-E. Cattin, A. T. Bertrand, S. Schlossarek, M.-C. Le Bihan, S. Skov Jensen, C. Neuber, C. Crocini, S. Maron, J. Laine, N. Mougenot, et al. (2013)
Hum. Mol. Genet. 22, 3152-3164
   Abstract »    Full Text »    PDF »
Ras Protein/cAMP-dependent Protein Kinase Signaling Is Negatively Regulated by a Deubiquitinating Enzyme, Ubp3, in Yeast.
Y. Li and Y. Wang (2013)
J. Biol. Chem. 288, 11358-11365
   Abstract »    Full Text »    PDF »
Role of the Ubiquitin Proteasome System in the Heart.
J. Pagan, T. Seto, M. Pagano, and A. Cittadini (2013)
Circ. Res. 112, 1046-1058
   Abstract »    Full Text »    PDF »
Distinct roles for {beta}-arrestin2 and arrestin-domain-containing proteins in {beta}2 adrenergic receptor trafficking.
S.-O. Han, R. P. Kommaddi, and S. K. Shenoy (2013)
EMBO Rep. 14, 164-171
   Abstract »    Full Text »    PDF »
MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound {beta}2-adrenergic receptors.
S.-o. Han, K. Xiao, J. Kim, J.-H. Wu, J. W. Wisler, N. Nakamura, N. J. Freedman, and S. K. Shenoy (2012)
J. Cell Biol. 199, 817-830
   Abstract »    Full Text »    PDF »
Induction of Cardiac Fibrosis by {beta}-Blocker in G Protein-independent and G Protein-coupled Receptor Kinase 5/{beta}-Arrestin2-dependent Signaling Pathways.
M. Nakaya, S. Chikura, K. Watari, N. Mizuno, K. Mochinaga, S. Mangmool, S. Koyanagi, S. Ohdo, Y. Sato, T. Ide, et al. (2012)
J. Biol. Chem. 287, 35669-35677
   Abstract »    Full Text »    PDF »
Role of Rhodopsin and Arrestin Phosphorylation in Retinal Degeneration of Drosophila.
I. Kristaponyte, Y. Hong, H. Lu, and B.-H. Shieh (2012)
J. Neurosci. 32, 10758-10766
   Abstract »    Full Text »    PDF »
Prostaglandin EP1 Receptor Down-regulates Expression of Cyclooxygenase-2 by Facilitating Its Proteasomal Degradation.
A. Haddad, G. Flint-Ashtamker, W. Minzel, R. Sood, G. Rimon, and L. Barki-Harrington (2012)
J. Biol. Chem. 287, 17214-17223
   Abstract »    Full Text »    PDF »
A novel EST-derived RNAi screen reveals a critical role for farnesyl diphosphate synthase in {beta}2-adrenergic receptor internalization and down-regulation.
X. Jiang, H. Pan, J. F. Nabhan, R. Krishnan, C. Koziol-White, R. A. Panettieri, and Q. Lu (2012)
FASEB J 26, 1995-2007
   Abstract »    Full Text »    PDF »
Fluorescence/Bioluminescence Resonance Energy Transfer Techniques to Study G-Protein-Coupled Receptor Activation and Signaling.
M. J. Lohse, S. Nuber, and C. Hoffmann (2012)
Pharmacol. Rev. 64, 299-336
   Abstract »    Full Text »    PDF »
The Role of {beta}-Arrestin2 in the Mechanism of Morphine Tolerance in the Mouse and Guinea Pig Gastrointestinal Tract.
M. Kang, H. T. Maguma, T. H. Smith, G. R. Ross, W. L. Dewey, and H. I. Akbarali (2012)
J. Pharmacol. Exp. Ther. 340, 567-576
   Abstract »    Full Text »    PDF »
The Regulation of Multiple p53 Stress Responses is Mediated through MDM2.
W. Hu, Z. Feng, and A. J. Levine (2012)
Genes & Cancer 3, 199-208
   Abstract »    Full Text »    PDF »
Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan.
S. Sigismund, S. Confalonieri, A. Ciliberto, S. Polo, G. Scita, and P. P. Di Fiore (2012)
Physiol Rev 92, 273-366
   Abstract »    Full Text »    PDF »
Ubiquitination in the First Cytoplasmic Loop of {mu}-Opioid Receptors Reveals a Hierarchical Mechanism of Lysosomal Down-regulation.
J. N. Hislop, A. G. Henry, and M. von Zastrow (2011)
J. Biol. Chem. 286, 40193-40204
   Abstract »    Full Text »    PDF »
Biochemical Basis of Asthma Therapy.
P. J. Barnes (2011)
J. Biol. Chem. 286, 32899-32905
   Abstract »    Full Text »    PDF »
Agonist-directed Interactions with Specific {beta}-Arrestins Determine {micro}-Opioid Receptor Trafficking, Ubiquitination, and Dephosphorylation.
C. E. Groer, C. L. Schmid, A. M. Jaeger, and L. M. Bohn (2011)
J. Biol. Chem. 286, 31731-31741
   Abstract »    Full Text »    PDF »
MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation.
C. A. Eyster, N. B. Cole, S. Petersen, K. Viswanathan, K. Fruh, and J. G. Donaldson (2011)
Mol. Biol. Cell 22, 3218-3230
   Abstract »    Full Text »    PDF »
The N Terminus of the Adhesion G Protein-coupled Receptor GPR56 Controls Receptor Signaling Activity.
K. J. Paavola, J. R. Stephenson, S. L. Ritter, S. P. Alter, and R. A. Hall (2011)
J. Biol. Chem. 286, 28914-28921
   Abstract »    Full Text »    PDF »
Distinct Phosphorylation Sites on the {beta}2-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of {beta}-Arrestin.
K. N. Nobles, K. Xiao, S. Ahn, A. K. Shukla, C. M. Lam, S. Rajagopal, R. T. Strachan, T.-Y. Huang, E. A. Bressler, M. R. Hara, et al. (2011)
Science Signaling 4, ra51
   Abstract »    Full Text »    PDF »
The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function.
F. Giordano, S. Simoes, and G. Raposo (2011)
PNAS 108, 11906-11911
   Abstract »    Full Text »    PDF »
Decreased Degradation of Internalized Follicle-Stimulating Hormone Caused by Mutation of Aspartic Acid 6.30550 in a Protein Kinase-CK2 Consensus Sequence in the Third Intracellular Loop of Human Follicle-Stimulating Hormone Receptor.
K. S. Kluetzman, R. M. Thomas, C. A. Nechamen, and J. A. Dias (2011)
Biol Reprod 84, 1154-1163
   Abstract »    Full Text »    PDF »
Temporal Profiling of Orexin Receptor-Arrestin-Ubiquitin Complexes Reveals Differences between Receptor Subtypes.
M. B. Dalrymple, W. C. Jaeger, K. A. Eidne, and K. D. G. Pfleger (2011)
J. Biol. Chem. 286, 16726-16733
   Abstract »    Full Text »    PDF »
Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of {beta}-arrestin2.
C. Yin, R. Zhang, Y. Xu, Q. Chen, and X. Xie (2011)
Mol. Biol. Cell 22, 1608-1616
   Abstract »    Full Text »    PDF »
S. R. Fuhs and P. A. Insel (2011)
J. Biol. Chem. 286, 14830-14841
   Abstract »    Full Text »    PDF »
{beta}2-Adrenergic Receptor Lysosomal Trafficking Is Regulated by Ubiquitination of Lysyl Residues in Two Distinct Receptor Domains.
K. Xiao and S. K. Shenoy (2011)
J. Biol. Chem. 286, 12785-12795
   Abstract »    Full Text »    PDF »
Cardiomyocyte lipids impair {beta}-adrenergic receptor function via PKC activation.
K. Drosatos, K. G. Bharadwaj, A. Lymperopoulos, S. Ikeda, R. Khan, Y. Hu, R. Agarwal, S. Yu, H. Jiang, S. F. Steinberg, et al. (2011)
Am J Physiol Endocrinol Metab 300, E489-E499
   Abstract »    Full Text »    PDF »
Small Ubiquitin-like Modifier Modification of Arrestin-3 Regulates Receptor Trafficking.
D. Wyatt, R. Malik, A. C. Vesecky, and A. Marchese (2011)
J. Biol. Chem. 286, 3884-3893
   Abstract »    Full Text »    PDF »
Multiple Scaffolding Functions of {beta}-Arrestins in the Degradation of G Protein-coupled Receptor Kinase 2.
L. Nogues, A. Salcedo, F. Mayor Jr., and P. Penela (2011)
J. Biol. Chem. 286, 1165-1173
   Abstract »    Full Text »    PDF »
Nedd4-1 and {beta}-Arrestin-1 Are Key Regulators of Na+/H+ Exchanger 1 Ubiquitylation, Endocytosis, and Function.
A. Simonin and D. Fuster (2010)
J. Biol. Chem. 285, 38293-38303
   Abstract »    Full Text »    PDF »
Quality control for unfolded proteins at the plasma membrane.
P. M. Apaja, H. Xu, and G. L. Lukacs (2010)
J. Cell Biol. 191, 553-570
   Abstract »    Full Text »    PDF »
Differential Regulation of Proteasome Function in Isoproterenol-Induced Cardiac Hypertrophy.
O. Drews, O. Tsukamoto, D. Liem, J. Streicher, Y. Wang, and P. Ping (2010)
Circ. Res. 107, 1094-1101
   Abstract »    Full Text »    PDF »
{alpha}-Arrestins Aly1 and Aly2 Regulate Intracellular Trafficking in Response to Nutrient Signaling.
A. F. O'Donnell, A. Apffel, R. G. Gardner, and M. S. Cyert (2010)
Mol. Biol. Cell 21, 3552-3566
   Abstract »    Full Text »    PDF »
Regulation of Mammalian Autophagy in Physiology and Pathophysiology.
B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-Arencibia, Z. W. Green-Thompson, M. Jimenez-Sanchez, V. I. Korolchuk, M. Lichtenberg, S. Luo, et al. (2010)
Physiol Rev 90, 1383-1435
   Abstract »    Full Text »    PDF »
A. K. Shukla, J. Kim, S. Ahn, K. Xiao, S. K. Shenoy, W. Liedtke, and R. J. Lefkowitz (2010)
J. Biol. Chem. 285, 30115-30125
   Abstract »    Full Text »    PDF »
Non-canonical Wnt Signaling Induces Ubiquitination and Degradation of Syndecan4.
L. Carvallo, R. Munoz, F. Bustos, N. Escobedo, H. Carrasco, G. Olivares, and J. Larrain (2010)
J. Biol. Chem. 285, 29546-29555
   Abstract »    Full Text »    PDF »
Arrestin-2 Interacts with the Endosomal Sorting Complex Required for Transport Machinery to Modulate Endosomal Sorting of CXCR4.
R. Malik and A. Marchese (2010)
Mol. Biol. Cell 21, 2529-2541
   Abstract »    Full Text »    PDF »
MDM2 Promotes Proteasomal Degradation of p21Waf1 via a Conformation Change.
H. Xu, Z. Zhang, M. Li, and R. Zhang (2010)
J. Biol. Chem. 285, 18407-18414
   Abstract »    Full Text »    PDF »
Beyond Desensitization: Physiological Relevance of Arrestin-Dependent Signaling.
L. M. Luttrell, D. Gesty-Palmer, and D. R. Sibley (2010)
Pharmacol. Rev. 62, 305-330
   Abstract »    Full Text »    PDF »
Phosphorylation of Protease-activated Receptor-2 Differentially Regulates Desensitization and Internalization.
T. K. Ricks and J. Trejo (2009)
J. Biol. Chem. 284, 34444-34457
   Abstract »    Full Text »    PDF »
Mahogunin Ring Finger-1 (MGRN1) E3 Ubiquitin Ligase Inhibits Signaling from Melanocortin Receptor by Competition with G{alpha}s.
A. B. Perez-Oliva, C. Olivares, C. Jimenez-Cervantes, and J. C. Garcia-Borron (2009)
J. Biol. Chem. 284, 31714-31725
   Abstract »    Full Text »    PDF »
Endosomes: A legitimate platform for the signaling train.
J. E. Murphy, B. E. Padilla, B. Hasdemir, G. S. Cottrell, and N. W. Bunnett (2009)
PNAS 106, 17615-17622
   Abstract »    Full Text »    PDF »
Endosomal Deubiquitinating Enzymes Control Ubiquitination and Down-regulation of Protease-activated Receptor 2.
B. Hasdemir, J. E. Murphy, G. S. Cottrell, and N. W. Bunnett (2009)
J. Biol. Chem. 284, 28453-28466
   Abstract »    Full Text »    PDF »
Novel Roles of Hakai in Cell Proliferation and Oncogenesis.
A. Figueroa, H. Kotani, Y. Toda, K. Mazan-Mamczarz, E.-C. Mueller, A. Otto, L. Disch, M. Norman, R. M. Ramdasi, M. Keshtgar, et al. (2009)
Mol. Biol. Cell 20, 3533-3542
   Abstract »    Full Text »    PDF »
Ubiquitination Regulates Proteolytic Processing of G Protein-coupled Receptors after Their Sorting to Lysosomes.
J. N. Hislop, A. G. Henry, A. Marchese, and M. von Zastrow (2009)
J. Biol. Chem. 284, 19361-19370
   Abstract »    Full Text »    PDF »
Oxygen-Regulated {beta}2-Adrenergic Receptor Hydroxylation by EGLN3 and Ubiquitylation by pVHL.
L. Xie, K. Xiao, E. J. Whalen, M. T. Forrester, R. S. Freeman, G. Fong, S. P. Gygi, R. J. Lefkowitz, and J. S. Stamler (2009)
Science Signaling 2, ra33
   Abstract »    Full Text »    PDF »
The deubiquitinases USP33 and USP20 coordinate {beta}2 adrenergic receptor recycling and resensitization.
M. Berthouze, V. Venkataramanan, Y. Li, and S. K. Shenoy (2009)
EMBO J. 28, 1684-1696
   Abstract »    Full Text »    PDF »
Mdm2 Directs the Ubiquitination of {beta}-Arrestin-sequestered cAMP Phosphodiesterase-4D5.
X. Li, G. S. Baillie, and M. D. Houslay (2009)
J. Biol. Chem. 284, 16170-16182
   Abstract »    Full Text »    PDF »
Identification of {beta}Arrestin2 as a corepressor of androgen receptor signaling in prostate cancer.
V. Lakshmikanthan, L. Zou, J. I. Kim, A. Michal, Z. Nie, N. C. Messias, J. L. Benovic, and Y. Daaka (2009)
PNAS 106, 9379-9384
   Abstract »    Full Text »    PDF »
{beta}-Arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2.
S. K. Shenoy, A. S. Modi, A. K. Shukla, K. Xiao, M. Berthouze, S. Ahn, K. D. Wilkinson, W. E. Miller, and R. J. Lefkowitz (2009)
PNAS 106, 6650-6655
   Abstract »    Full Text »    PDF »
The 27-kDa Heat Shock Protein Confers Cytoprotective Effects through a {beta}2-Adrenergic Receptor Agonist-Initiated Complex with {beta}-Arrestin.
L. Rojanathammanee, E. B. Harmon, L. A. Grisanti, P. Govitrapong, M. Ebadi, B. D. Grove, M. Miyagi, and J. E. Porter (2009)
Mol. Pharmacol. 75, 855-865
   Abstract »    Full Text »    PDF »
G Protein Mono-ubiquitination by the Rsp5 Ubiquitin Ligase.
M. P. Torres, M. J. Lee, F. Ding, C. Purbeck, B. Kuhlman, N. V. Dokholyan, and H. G. Dohlman (2009)
J. Biol. Chem. 284, 8940-8950
   Abstract »    Full Text »    PDF »
The E3 Ubiquitin Ligase Atrophin Interacting Protein 4 Binds Directly To The Chemokine Receptor CXCR4 Via a Novel WW Domain-mediated Interaction.
D. Bhandari, S. L. Robia, and A. Marchese (2009)
Mol. Biol. Cell 20, 1324-1339
   Abstract »    Full Text »    PDF »
How Does Arrestin Assemble MAPKs into a Signaling Complex?.
X. Song, S. Coffa, H. Fu, and V. V. Gurevich (2009)
J. Biol. Chem. 284, 685-695
   Abstract »    Full Text »    PDF »
The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis.
P. J. Baugher and A. Richmond (2008)
J. Biol. Chem. 283, 30868-30878
   Abstract »    Full Text »    PDF »
MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation.
G. Chen, H. Huang, O. Frohlich, Y. Yang, J. D. Klein, S. R. Price, and J. M. Sands (2008)
Am J Physiol Renal Physiol 295, F1528-F1534
   Abstract »    Full Text »    PDF »
Arrestin 3 Mediates Endocytosis of CCR7 following Ligation of CCL19 but Not CCL21.
M. A. Byers, P. A. Calloway, L. Shannon, H. D. Cunningham, S. Smith, F. Li, B. C. Fassold, and C. M. Vines (2008)
J. Immunol. 181, 4723-4732
   Abstract »    Full Text »    PDF »
Nedd4 Mediates Agonist-dependent Ubiquitination, Lysosomal Targeting, and Degradation of the {beta}2-Adrenergic Receptor.
S. K. Shenoy, K. Xiao, V. Venkataramanan, P. M. Snyder, N. J. Freedman, and A. M. Weissman (2008)
J. Biol. Chem. 283, 22166-22176
   Abstract »    Full Text »    PDF »
Site-specific Cleavage of G Protein-coupled Receptor-engaged {beta}-Arrestin: INFLUENCE OF THE AT1 RECEPTOR CONFORMATION ON SCISSILE SITE SELECTION.
C. Lee, S. Bhatt, A. Shukla, R. W. Desnoyer, S. P. Yadav, M. Kim, S.-H. Jang, and S. S. Karnik (2008)
J. Biol. Chem. 283, 21612-21620
   Abstract »    Full Text »    PDF »
{beta}-Arrestin Scaffolding of Phosphatidylinositol 4-Phosphate 5-Kinase I{alpha} Promotes Agonist-stimulated Sequestration of the {beta}2-Adrenergic Receptor.
C. D. Nelson, J. J. Kovacs, K. N. Nobles, E. J. Whalen, and R. J. Lefkowitz (2008)
J. Biol. Chem. 283, 21093-21101
   Abstract »    Full Text »    PDF »
Guanine exchange factor RalGDS mediates exocytosis of Weibel-Palade bodies from endothelial cells.
M. G. Rondaij, R. Bierings, E. L. van Agtmaal, K. A. Gijzen, E. Sellink, A. Kragt, S. S. G. Ferguson, K. Mertens, M. J. Hannah, J. A. van Mourik, et al. (2008)
Blood 112, 56-63
   Abstract »    Full Text »    PDF »
Lysine 144, a Ubiquitin Attachment Site in HIV-1 Nef, Is Required for Nef-Mediated CD4 Down-Regulation.
Y.-J. Jin, C. Y. Cai, X. Zhang, and S. J. Burakoff (2008)
J. Immunol. 180, 7878-7886
   Abstract »    Full Text »    PDF »
Opposite Regulation of CD36 Ubiquitination by Fatty Acids and Insulin: EFFECTS ON FATTY ACID UPTAKE.
J. Smith, X. Su, R. El-Maghrabi, P. D. Stahl, and N. A. Abumrad (2008)
J. Biol. Chem. 283, 13578-13585
   Abstract »    Full Text »    PDF »
{beta}-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic {beta} cells.
N. Sonoda, T. Imamura, T. Yoshizaki, J. L. Babendure, J.-C. Lu, and J. M. Olefsky (2008)
PNAS 105, 6614-6619
   Abstract »    Full Text »    PDF »
MDM2 Regulates Dihydrofolate Reductase Activity through Monoubiquitination.
M. Maguire, P. C. Nield, T. Devling, R. E. Jenkins, B. K. Park, R. Polanski, N. Vlatkovic, and M. T. Boyd (2008)
Cancer Res. 68, 3232-3242
   Abstract »    Full Text »    PDF »
BTB Protein KLHL12 Targets the Dopamine D4 Receptor for Ubiquitination by a Cul3-based E3 Ligase.
P. Rondou, G. Haegeman, P. Vanhoenacker, and K. Van Craenenbroeck (2008)
J. Biol. Chem. 283, 11083-11096
   Abstract »    Full Text »    PDF »
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury.
E. Murphy and C. Steenbergen (2008)
Physiol Rev 88, 581-609
   Abstract »    Full Text »    PDF »
Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease.
G. S. Lynch and J. G. Ryall (2008)
Physiol Rev 88, 729-767
   Abstract »    Full Text »    PDF »
Agonist-Promoted Lys63-Linked Polyubiquitination of the Human {kappa}-Opioid Receptor Is Involved in Receptor Down-Regulation.
J.-G. Li, D. S. Haines, and L.-Y. Liu-Chen (2008)
Mol. Pharmacol. 73, 1319-1330
   Abstract »    Full Text »    PDF »
The Ubiquitin-like Protein PLIC-2 Is a Negative Regulator of G Protein-coupled Receptor Endocytosis.
E.-N. N'Diaye, A. C. Hanyaloglu, K. K. Kajihara, M. A. Puthenveedu, P. Wu, M. von Zastrow, and E. J. Brown (2008)
Mol. Biol. Cell 19, 1252-1260
   Abstract »    Full Text »    PDF »
{beta}-Arrestins: Multifunctional Cellular Mediators.
L. Barki-Harrington and H. A. Rockman (2008)
Physiology 23, 17-22
   Abstract »    Full Text »    PDF »
The Lysophosphatidic Acid 2 Receptor Mediates Down-regulation of Siva-1 to Promote Cell Survival.
F.-T. Lin, Y.-J. Lai, N. Makarova, G. Tigyi, and W.-C. Lin (2007)
J. Biol. Chem. 282, 37759-37769
   Abstract »    Full Text »    PDF »
Arrestin-2 Interacts with the Ubiquitin-Protein Isopeptide Ligase Atrophin-interacting Protein 4 and Mediates Endosomal Sorting of the Chemokine Receptor CXCR4.
D. Bhandari, J. Trejo, J. L. Benovic, and A. Marchese (2007)
J. Biol. Chem. 282, 36971-36979
   Abstract »    Full Text »    PDF »
A Proteomics Analysis of Cell Signaling Alterations in Colorectal Cancer.
J. Madoz-Gurpide, M. Canamero, L. Sanchez, J. Solano, P. Alfonso, and J. I. Casal (2007)
Mol. Cell. Proteomics 6, 2150-2164
   Abstract »    Full Text »    PDF »
Identification of a Postendocytic Sorting Sequence in CCR5.
M. Delhaye, A. Gravot, D. Ayinde, F. Niedergang, M. Alizon, and A. Brelot (2007)
Mol. Pharmacol. 72, 1497-1507
   Abstract »    Full Text »    PDF »
{beta}-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53.
C. Boularan, M. G. H. Scott, K. Bourougaa, M. Bellal, E. Esteve, A. Thuret, A. Benmerah, M. Tramier, M. Coppey-Moisan, C. Labbe-Jullie, et al. (2007)
PNAS 104, 18061-18066
   Abstract »    Full Text »    PDF »
Ubiquitination of beta-Arrestin Links Seven-transmembrane Receptor Endocytosis and ERK Activation.
S. K. Shenoy, L. S. Barak, K. Xiao, S. Ahn, M. Berthouze, A. K. Shukla, L. M. Luttrell, and R. J. Lefkowitz (2007)
J. Biol. Chem. 282, 29549-29562
   Abstract »    Full Text »    PDF »
Plasticity of Polyubiquitin Recognition as Lysosomal Targeting Signals by the Endosomal Sorting Machinery.
H. Barriere, C. Nemes, K. Du, and G. L. Lukacs (2007)
Mol. Biol. Cell 18, 3952-3965
   Abstract »    Full Text »    PDF »
Nedd4-2 Catalyzes Ubiquitination and Degradation of Cell Surface ENaC.
R. Zhou, S. V. Patel, and P. M. Snyder (2007)
J. Biol. Chem. 282, 20207-20212
   Abstract »    Full Text »    PDF »
The Ubiquitin Ligase SCF(betaTrCP) Regulates the Degradation of the Growth Hormone Receptor.
P. van Kerkhof, J. Putters, and G. J. Strous (2007)
J. Biol. Chem. 282, 20475-20483
   Abstract »    Full Text »    PDF »
Differential effects of beta-arrestins on the internalization, desensitization and ERK1/2 activation downstream of protease activated receptor-2.
P. Kumar, C. S. Lau, M. Mathur, P. Wang, and K. A. DeFea (2007)
Am J Physiol Cell Physiol 293, C346-C357
   Abstract »    Full Text »    PDF »
Ubiquitination differentially regulates clathrin-dependent internalization of protease-activated receptor-1.
B. L. Wolfe, A. Marchese, and J. Trejo (2007)
J. Cell Biol. 177, 905-916
   Abstract »    Full Text »    PDF »
Proteasome-Regulated ERBB2 and Estrogen Receptor Pathways in Breast Cancer.
C. Marx, C. Yau, S. Banwait, Y. Zhou, G. K. Scott, B. Hann, J. W. Park, and C. C. Benz (2007)
Mol. Pharmacol. 71, 1525-1534
   Abstract »    Full Text »    PDF »
Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.
H. Shi, C. Zeng, A. Ricome, K. M. Hannon, A. L. Grant, and D. E. Gerrard (2007)
Am J Physiol Cell Physiol 292, C1681-C1689
   Abstract »    Full Text »    PDF »
Seven-Transmembrane Receptors and Ubiquitination.
S. K. Shenoy (2007)
Circ. Res. 100, 1142-1154
   Abstract »    Full Text »    PDF »
Post-endocytic Sorting of Calcitonin Receptor-like Receptor and Receptor Activity-modifying Protein 1.
G. S. Cottrell, B. Padilla, S. Pikios, D. Roosterman, M. Steinhoff, E. F. Grady, and N. W. Bunnett (2007)
J. Biol. Chem. 282, 12260-12271
   Abstract »    Full Text »    PDF »
beta-Arrestin and Mdm2 Mediate IGF-1 Receptor-stimulated ERK Activation and Cell Cycle Progression.
L. Girnita, S. K. Shenoy, B. Sehat, R. Vasilcanu, D. Vasilcanu, A. Girnita, R. J. Lefkowitz, and O. Larsson (2007)
J. Biol. Chem. 282, 11329-11338
   Abstract »    Full Text »    PDF »
Novel insights in somatostatin receptor physiology.
G. Tulipano and S. Schulz (2007)
Eur. J. Endocrinol. 156, S3-S11
   Abstract »    Full Text »    PDF »
Immunosuppressive and Anti-angiogenic Sphingosine 1-Phosphate Receptor-1 Agonists Induce Ubiquitinylation and Proteasomal Degradation of the Receptor.
M. L. Oo, S. Thangada, M.-T. Wu, C. H. Liu, T. L. Macdonald, K. R. Lynch, C.-Y. Lin, and T. Hla (2007)
J. Biol. Chem. 282, 9082-9089
   Abstract »    Full Text »    PDF »
Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer.
P. Arora, T. K. Ricks, and J. Trejo (2007)
J. Cell Sci. 120, 921-928
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882