Home LiteratureArticle Details
PMID: 23201781 Published · ppublish English Journal Article Review

Ubiquitin-dependent regulation of G protein-coupled receptor trafficking and signaling.

Cellular signalling ·Vol. 25 ·No. 3 ·2013-03-00 ·Pages 707-16

Marchese A, Trejo J

Abstract

G protein-coupled receptors (GPCRs) belong to one of the largest family of signaling receptors in the mammalian genome [1]. GPCRs elicit cellular responses to multiple diverse stimuli and play essential roles in human health and disease. GPCRs have important clinical implications in various diseases and are the targets of approximately 25-50% of all marketed drugs [2,3]. Understanding how GPCRs are regulated is essential to delineating their role in normal physiology and in the pathophysiology of several diseases. Given the vast number and diversity of GPCRs, it is likely that multiple mechanisms exist to regulate GPCR function. While GPCR signaling is typically regulated by desensitization and endocytosis mediated by phosphorylation and β-arrestins, it can also be modulated by ubiquitination. Ubiquitination is emerging an important regulatory process that may have unique roles in governing GPCR trafficking and signaling. Recent studies have revealed a mechanistic link between GPCR phosphorylation, β-arrestins and ubiquitination that may be applicable to some GPCRs but not others. While the function of ubiquitination is generally thought to promote receptor endocytosis and endosomal sorting, recent studies have revealed that ubiquitination also plays an important role in positive regulation of GPCR signaling. Here, we will review recent developments in our understanding of how ubiquitin regulates GPCR endocytic trafficking and how it contributes to signal transduction induced by GPCR activation.

MeSH Terms
Arrestins/metabolism Endosomal Sorting Complexes Required for Transport/metabolism Humans Receptors, Adrenergic, beta-2/metabolism Receptors, CXCR4/metabolism Receptors, G-Protein-Coupled/metabolism Receptors, Opioid/metabolism Signal Transduction Ubiquitin/metabolism Ubiquitination beta-Arrestins
Chemicals
Arrestins CXCR4 protein, human Endosomal Sorting Complexes Required for Transport Receptors, Adrenergic, beta-2 Receptors, CXCR4 Receptors, G-Protein-Coupled Receptors, Opioid Ubiquitin beta-Arrestins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Marchese Adriano
Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, 2160 S. 1st Ave., Building 101, Room 2721, Maywood, IL 60153, USA. amarchese@lumc.edu
Trejo Joann
References (138)
138 references, click to expand
  1. AMSH interacts with ESCRT-0 to regulate the stability and trafficking of CXCR4.
    J Biol Chem. 2010 Apr 30;285(18):13990-4004 PMID: 20159979
  2. Agonist-directed interactions with specific beta-arrestins determine mu-opioid receptor trafficking, ubiquitination, and dephosphorylation.
    J Biol Chem. 2011 Sep 9;286(36):31731-41 PMID: 21757712
  3. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
    J Cell Biol. 2012 Apr 30;197(3):407-19 PMID: 22547407
  4. Pias1 interaction and sumoylation of metabotropic glutamate receptor 8.
    J Biol Chem. 2005 Nov 18;280(46):38153-9 PMID: 16144832
  5. Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2.
    Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6650-5 PMID: 19363159
  6. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins.
    Science. 2002 Oct 25;298(5594):834-6 PMID: 12399592
  7. International Union of Pharmacology. XLVI. G protein-coupled receptor list.
    Pharmacol Rev. 2005 Jun;57(2):279-88 PMID: 15914470
  8. Structural and functional studies of ALIX interactions with YPX(n)L late domains of HIV-1 and EIAV.
    Nat Struct Mol Biol. 2008 Jan;15(1):43-9 PMID: 18066081
  9. The type I TGF-beta receptor is covalently modified and regulated by sumoylation.
    Nat Cell Biol. 2008 Jun;10(6):654-64 PMID: 18469808
  10. Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor.
    J Biol Chem. 2007 Oct 5;282(40):29646-57 PMID: 17675298
  11. The ESCRT pathway.
    Dev Cell. 2011 Jul 19;21(1):77-91 PMID: 21763610
  12. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.
    Cell. 2001 Oct 5;107(1):55-65 PMID: 11595185
  13. Novel roles for the E3 ubiquitin ligase atrophin-interacting protein 4 and signal transduction adaptor molecule 1 in G protein-coupled receptor signaling.
    J Biol Chem. 2012 Mar 16;287(12):9013-27 PMID: 22275353
  14. Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization.
    J Cell Biol. 1998 Apr 20;141(2):349-58 PMID: 9548714
  15. Protein modification by SUMO.
    Annu Rev Biochem. 2004;73:355-82 PMID: 15189146
  16. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I.
    Cell. 2001 Jul 27;106(2):145-55 PMID: 11511343
  17. The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction.
    Mol Biol Cell. 2009 Mar;20(5):1324-39 PMID: 19116316
  18. β-Arrestin-mediated receptor trafficking and signal transduction.
    Trends Pharmacol Sci. 2011 Sep;32(9):521-33 PMID: 21680031
  19. Receptor-specific ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes.
    J Biol Chem. 2005 Apr 15;280(15):15315-24 PMID: 15699045
  20. Morphine-activated opioid receptors elude desensitization by beta-arrestin.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9914-9 PMID: 9707575
  21. Arrestin-2 interacts with the ubiquitin-protein isopeptide ligase atrophin-interacting protein 4 and mediates endosomal sorting of the chemokine receptor CXCR4.
    J Biol Chem. 2007 Dec 21;282(51):36971-9 PMID: 17947233
  22. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation.
    Cell. 1991 Mar 22;64(6):1057-68 PMID: 1672265
  23. G protein-coupled receptor sorting to endosomes and lysosomes.
    Annu Rev Pharmacol Toxicol. 2008;48:601-29 PMID: 17995450
  24. The nuts and bolts of AGC protein kinases.
    Nat Rev Mol Cell Biol. 2010 Jan;11(1):9-22 PMID: 20027184
  25. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4.
    Dev Cell. 2003 Nov;5(5):709-22 PMID: 14602072
  26. Molecular mechanisms of ubiquitin-dependent membrane traffic.
    Annu Rev Biophys. 2011;40:119-42 PMID: 21332354
  27. Ubiquitin and ubiquitin-like proteins in cancer pathogenesis.
    Nat Rev Cancer. 2006 Oct;6(10):776-88 PMID: 16990855
  28. Type-specific sorting of G protein-coupled receptors after endocytosis.
    J Biol Chem. 2000 Apr 14;275(15):11130-40 PMID: 10753919
  29. On the origins of arrestin and rhodopsin.
    BMC Evol Biol. 2008 Jul 29;8:222 PMID: 18664266
  30. The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture.
    Oncogene. 2004 Mar 15;23(11):1972-84 PMID: 15021885
  31. Regulation of receptor trafficking by GRKs and arrestins.
    Annu Rev Physiol. 2007;69:451-82 PMID: 17037978
  32. Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting.
    Dev Cell. 2002 Aug;3(2):271-82 PMID: 12194857
  33. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis.
    EMBO J. 2007 Oct 3;26(19):4215-27 PMID: 17853893
  34. Ubiquitination of CXCR7 controls receptor trafficking.
    PLoS One. 2012;7(3):e34192 PMID: 22457824
  35. Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination.
    J Biol Chem. 2003 Apr 18;278(16):14498-506 PMID: 12574160
  36. Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation.
    J Biol Chem. 2009 Feb 27;284(9):5742-52 PMID: 19106094
  37. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3712-7 PMID: 10097102
  38. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.
    Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10782-7 PMID: 12949261
  39. The ESCRT complexes.
    Crit Rev Biochem Mol Biol. 2010 Dec;45(6):463-87 PMID: 20653365
  40. Arrestins: ubiquitous regulators of cellular signaling pathways.
    Genome Biol. 2006;7(9):236 PMID: 17020596
  41. WW and SH3 domains, two different scaffolds to recognize proline-rich ligands.
    FEBS Lett. 2002 Feb 20;513(1):30-7 PMID: 11911877
  42. The spatial and temporal organization of ubiquitin networks.
    Nat Rev Mol Cell Biol. 2011 May;12(5):295-307 PMID: 21448225
  43. c-Cbl mediates ubiquitination, degradation, and down-regulation of human protease-activated receptor 2.
    J Biol Chem. 2005 Apr 22;280(16):16076-87 PMID: 15708858
  44. ESCRT complexes and the biogenesis of multivesicular bodies.
    Curr Opin Cell Biol. 2008 Feb;20(1):4-11 PMID: 18222686
  45. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor.
    Nature. 1996 Oct 3;383(6599):447-50 PMID: 8837779
  46. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes.
    Nat Cell Biol. 2002 May;4(5):394-8 PMID: 11988743
  47. Role of mammalian vacuolar protein-sorting proteins in endocytic trafficking of a non-ubiquitinated G protein-coupled receptor to lysosomes.
    J Biol Chem. 2004 May 21;279(21):22522-31 PMID: 15024011
  48. The biogenesis of multivesicular endosomes.
    Nat Rev Mol Cell Biol. 2004 Apr;5(4):317-23 PMID: 15071556
  49. Role of ubiquitin- and Ubl-binding proteins in cell signaling.
    Curr Opin Cell Biol. 2007 Apr;19(2):199-205 PMID: 17303403
  50. Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.
    Annu Rev Pharmacol Toxicol. 2012;52:179-97 PMID: 21942629
  51. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.
    Cancer Cell. 2004 Nov;6(5):459-69 PMID: 15542430
  52. The Cbl interactome and its functions.
    Nat Rev Mol Cell Biol. 2005 Dec;6(12):907-18 PMID: 16227975
  53. beta-Arrestin: a protein that regulates beta-adrenergic receptor function.
    Science. 1990 Jun 22;248(4962):1547-50 PMID: 2163110
  54. Ubiquitin-binding domains.
    Nat Rev Mol Cell Biol. 2005 Aug;6(8):610-21 PMID: 16064137
  55. Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes.
    J Cell Biol. 2003 Aug 4;162(3):435-42 PMID: 12900395
  56. Modification of proteins by ubiquitin and ubiquitin-like proteins.
    Annu Rev Cell Dev Biol. 2006;22:159-80 PMID: 16753028
  57. Regulation of endocytic clathrin dynamics by cargo ubiquitination.
    Dev Cell. 2012 Sep 11;23(3):519-32 PMID: 22940114
  58. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body.
    Dev Cell. 2002 Aug;3(2):283-9 PMID: 12194858
  59. Ubiquitin and membrane protein turnover: from cradle to grave.
    Annu Rev Biochem. 2012;81:231-59 PMID: 22404628
  60. Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor.
    J Biol Chem. 2004 Aug 20;279(34):35518-25 PMID: 15205453
  61. The cytoplasmic tails of protease-activated receptor-1 and substance P receptor specify sorting to lysosomes versus recycling.
    J Biol Chem. 1999 Jan 22;274(4):2216-24 PMID: 9890984
  62. P300 transcriptional repression is mediated by SUMO modification.
    Mol Cell. 2003 Apr;11(4):1043-54 PMID: 12718889
  63. Membrane scission by the ESCRT-III complex.
    Nature. 2009 Mar 12;458(7235):172-7 PMID: 19234443
  64. Arrestin-2 interacts with the endosomal sorting complex required for transport machinery to modulate endosomal sorting of CXCR4.
    Mol Biol Cell. 2010 Jul 15;21(14):2529-41 PMID: 20505072
  65. A map of WW domain family interactions.
    Proteomics. 2004 Mar;4(3):643-55 PMID: 14997488
  66. The role of receptor kinases and arrestins in G protein-coupled receptor regulation.
    Annu Rev Pharmacol Toxicol. 1998;38:289-319 PMID: 9597157
  67. Cbl: many adaptations to regulate protein tyrosine kinases.
    Nat Rev Mol Cell Biol. 2001 Apr;2(4):294-307 PMID: 11283727
  68. Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins.
    Science. 2007 Feb 2;315(5812):663-6 PMID: 17272726
  69. CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4.
    EMBO J. 2006 Aug 23;25(16):3738-49 PMID: 16888620
  70. Membrane budding.
    Cell. 2010 Dec 10;143(6):875-87 PMID: 21145455
  71. Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation.
    Mol Pharmacol. 2008 Apr;73(4):1319-30 PMID: 18212250
  72. Hybrid structural model of the complete human ESCRT-0 complex.
    Structure. 2009 Mar 11;17(3):406-16 PMID: 19278655
  73. Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor.
    Mol Cell. 1999 Jan;3(1):11-21 PMID: 10024875
  74. Ubiquitination differentially regulates clathrin-dependent internalization of protease-activated receptor-1.
    J Cell Biol. 2007 Jun 4;177(5):905-16 PMID: 17535965
  75. Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus.
    Genetics. 1995 May;140(1):255-65 PMID: 7635290
  76. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation.
    Cell. 2009 Mar 20;136(6):1098-109 PMID: 19303852
  77. Mechanism and function of deubiquitinating enzymes.
    Biochim Biophys Acta. 2004 Nov 29;1695(1-3):189-207 PMID: 15571815
  78. The carboxyl-terminal PDZ ligand motif of chemokine receptor CXCR2 modulates post-endocytic sorting and cellular chemotaxis.
    J Biol Chem. 2008 Nov 7;283(45):30868-78 PMID: 18755694
  79. Heterotrimeric G protein activation by G-protein-coupled receptors.
    Nat Rev Mol Cell Biol. 2008 Jan;9(1):60-71 PMID: 18043707
  80. A genomic and functional inventory of deubiquitinating enzymes.
    Cell. 2005 Dec 2;123(5):773-86 PMID: 16325574
  81. Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes.
    Mol Biol Cell. 2002 Mar;13(3):1071-82 PMID: 11907283
  82. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2563-7 PMID: 7708685
  83. AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding.
    Cell. 2003 Sep 19;114(6):689-99 PMID: 14505569
  84. An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins.
    Mol Biol Cell. 2006 Mar;17(3):1228-38 PMID: 16407403
  85. The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation.
    J Biol Chem. 2003 Feb 21;278(8):6258-67 PMID: 12473660
  86. Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor.
    J Biol Chem. 2008 Aug 8;283(32):22166-76 PMID: 18544533
  87. Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2.
    J Biol Chem. 2009 Oct 9;284(41):28453-28466 PMID: 19684015
  88. Beta2-adrenergic receptor lysosomal trafficking is regulated by ubiquitination of lysyl residues in two distinct receptor domains.
    J Biol Chem. 2011 Apr 8;286(14):12785-95 PMID: 21330366
  89. PI3K signalling: the path to discovery and understanding.
    Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):195-203 PMID: 22358332
  90. Ubiquitin-binding domains - from structures to functions.
    Nat Rev Mol Cell Biol. 2009 Oct;10(10):659-71 PMID: 19773779
  91. Identification of a novel sequence mediating regulated endocytosis of the G protein-coupled alpha-pheromone receptor in yeast.
    Mol Biol Cell. 1993 May;4(5):511-21 PMID: 8392878
  92. Structural basis for viral late-domain binding to Alix.
    Nat Struct Mol Biol. 2007 Mar;14(3):194-9 PMID: 17277784
  93. The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization.
    EMBO J. 2009 Jun 17;28(12):1684-96 PMID: 19424180
  94. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.
    Cell. 2008 Nov 14;135(4):714-25 PMID: 18976803
  95. Multiple roles for Rsp5p-dependent ubiquitination at the internalization step of endocytosis.
    J Biol Chem. 2001 Jul 13;276(28):25974-81 PMID: 11356856
  96. AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway.
    Mol Biol Cell. 2012 Sep;23(18):3612-23 PMID: 22833563
  97. The chemokine receptor CXCR3 is degraded following internalization and is replenished at the cell surface by de novo synthesis of receptor.
    J Immunol. 2008 May 15;180(10):6713-24 PMID: 18453591
  98. Regulation of monoubiquitinated PCNA by DUB autocleavage.
    Nat Cell Biol. 2006 Apr;8(4):339-47 PMID: 16531995
  99. HECT and RING finger families of E3 ubiquitin ligases at a glance.
    J Cell Sci. 2012 Feb 1;125(Pt 3):531-7 PMID: 22389392
  100. Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13698-702 PMID: 9811863
  101. The deubiquitinating enzyme USP8 promotes trafficking and degradation of the chemokine receptor 4 at the sorting endosome.
    J Biol Chem. 2010 Nov 26;285(48):37895-908 PMID: 20876529
  102. Ubiquitination in the first cytoplasmic loop of μ-opioid receptors reveals a hierarchical mechanism of lysosomal down-regulation.
    J Biol Chem. 2011 Nov 18;286(46):40193-204 PMID: 21953467
  103. The role of ubiquitination in lysosomal trafficking of δ-opioid receptors.
    Traffic. 2011 Feb;12(2):170-84 PMID: 21106040
  104. Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor.
    EMBO Rep. 2010 Aug;11(8):605-11 PMID: 20559325
  105. FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes.
    J Cell Sci. 2001 Jun;114(Pt 12):2255-63 PMID: 11493665
  106. Seven transmembrane receptors: something old, something new.
    Acta Physiol (Oxf). 2007 May;190(1):9-19 PMID: 17428228
  107. Molecular bases for the recognition of tyrosine-based sorting signals.
    J Cell Biol. 1999 May 31;145(5):923-6 PMID: 10352010
  108. ScanProsite: a reference implementation of a PROSITE scanning tool.
    Appl Bioinformatics. 2002;1(2):107-8 PMID: 15130850
  109. Modulation of postendocytic sorting of G protein-coupled receptors.
    Science. 2002 Jul 26;297(5581):615-20 PMID: 12142540
  110. The druggable genome.
    Nat Rev Drug Discov. 2002 Sep;1(9):727-30 PMID: 12209152
  111. Vps27 recruits ESCRT machinery to endosomes during MVB sorting.
    J Cell Biol. 2003 Aug 4;162(3):413-23 PMID: 12900393
  112. Isoform-specific localization of the deubiquitinase USP33 to the Golgi apparatus.
    Traffic. 2011 Nov;12(11):1563-74 PMID: 21801292
  113. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice.
    Nat Genet. 1998 Feb;18(2):143-6 PMID: 9462742
  114. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation.
    Nat Cell Biol. 2009 Feb;11(2):123-32 PMID: 19136968
  115. Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis.
    Nat Cell Biol. 2002 May;4(5):389-93 PMID: 11988742
  116. Function of WW domains as phosphoserine- or phosphothreonine-binding modules.
    Science. 1999 Feb 26;283(5406):1325-8 PMID: 10037602
  117. Beta-arrestins and cell signaling.
    Annu Rev Physiol. 2007;69:483-510 PMID: 17305471
  118. Ubiquitin-binding domains.
    Biochem J. 2006 Nov 1;399(3):361-72 PMID: 17034365
  119. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis.
    Cell. 1996 Jan 26;84(2):277-87 PMID: 8565073
  120. Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways.
    Dev Cell. 2009 Oct;17(4):443-58 PMID: 19853559
  121. Role for G protein-coupled receptor kinase in agonist-specific regulation of mu-opioid receptor responsiveness.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7157-62 PMID: 9618555
  122. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds.
    Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2449-54 PMID: 11226259
  123. Ubiquitin: structures, functions, mechanisms.
    Biochim Biophys Acta. 2004 Nov 29;1695(1-3):55-72 PMID: 15571809
  124. VHS domains of ESCRT-0 cooperate in high-avidity binding to polyubiquitinated cargo.
    EMBO J. 2010 Mar 17;29(6):1045-54 PMID: 20150893
  125. Drug discovery: a historical perspective.
    Science. 2000 Mar 17;287(5460):1960-4 PMID: 10720314
  126. LUBAC regulates NF-κB activation upon genotoxic stress by promoting linear ubiquitination of NEMO.
    EMBO J. 2011 Aug 02;30(18):3741-53 PMID: 21811235
  127. Involvement of chemokine receptors in breast cancer metastasis.
    Nature. 2001 Mar 1;410(6824):50-6 PMID: 11242036
  128. The C2 domain of the Rsp5 ubiquitin ligase binds membrane phosphoinositides and directs ubiquitination of endosomal cargo.
    J Cell Biol. 2004 Apr;165(1):135-44 PMID: 15078904
  129. Physiological functions of the HECT family of ubiquitin ligases.
    Nat Rev Mol Cell Biol. 2009 Jun;10(6):398-409 PMID: 19436320
  130. Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation.
    J Biol Chem. 2007 Oct 5;282(40):29549-62 PMID: 17666399
  131. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin.
    Science. 2001 Nov 9;294(5545):1307-13 PMID: 11588219
  132. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
    Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 PMID: 9396791
  133. Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling.
    J Biol Chem. 2010 Mar 5;285(10):7805-17 PMID: 20048153
  134. Small ubiquitin-like modifier modification of arrestin-3 regulates receptor trafficking.
    J Biol Chem. 2011 Feb 4;286(5):3884-93 PMID: 21118812
  135. Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks.
    Nature. 2009 Dec 17;462(7275):935-9 PMID: 20016603
  136. Ubiquitination regulates proteolytic processing of G protein-coupled receptors after their sorting to lysosomes.
    J Biol Chem. 2009 Jul 17;284(29):19361-70 PMID: 19433584
  137. Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting.
    J Biol Chem. 2001 Dec 7;276(49):45509-12 PMID: 11641392
  138. Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes.
    Mol Biol Cell. 2002 Apr;13(4):1313-28 PMID: 11950941
Article Info
Journal
Cellular signalling
Abbr.
Cell Signal
ISSN
1873-3913
DOI
10.1016/j.cellsig.2012.11.024
Email
amarchese@lumc.edu
Published
2013-03-00
Epub
2012-00-29
Pages
707-16
Language
English
Region
England
NLM ID
8904683
PMCID
PMC3593103
Subset
IM
Grants
NIGMS NIH HHS · R01 GM075159 · United States
External Links
PubMed source DOI: 10.1016/j.cellsig.2012.11.024 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2