Ubiquitination regulates the internalization, endolysosomal sorting, and signaling of the erythropoietin receptor.

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  • Author(s): Bulut GB;Bulut GB; Sulahian R; Ma Y; Chi NW; Huang LJ
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2011 Feb 25; Vol. 286 (8), pp. 6449-57. Date of Electronic Publication: 2010 Dec 23.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Endosomes/*metabolism ; Receptors, Erythropoietin/*metabolism ; Signal Transduction/*physiology ; Ubiquitination/*physiology; Animals ; Down-Regulation/physiology ; Endosomes/genetics ; Mice ; Mitogen-Activated Protein Kinase Kinases/genetics ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Transport/physiology ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Erythropoietin/genetics ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism ; ras Proteins/genetics ; ras Proteins/metabolism
    • Abstract:
      Ubiquitination is a common mechanism of down-regulation of mitogenic receptors. Here, we show that ubiquitination of the erythropoietin receptor (EpoR) at Lys(256) is necessary and sufficient for efficient Epo-induced receptor internalization, whereas ubiquitination at Lys(428) promotes trafficking of activated receptors to the lysosomes for degradation. Interestingly, EpoR that cannot be ubiquitinated has reduced mitogenic activities and ability to stimulate the STAT5, Ras/MAPK, and PI3K/AKT signaling pathways. We therefore propose that ubiquitination of the EpoR critically controls both receptor down-regulation and downstream signaling.
    • References:
      Blood. 2009 May 21;113(21):5287-97. (PMID: 19336760)
      J Biol Chem. 1993 Jun 25;268(18):13639-49. (PMID: 8514796)
      Mol Cell Biol. 2008 Aug;28(15):4805-18. (PMID: 18519587)
      Cell. 1998 May 1;93(3):385-95. (PMID: 9590173)
      Mol Biol Cell. 2007 Oct;18(10):3952-65. (PMID: 17686993)
      Cell. 1995 Oct 6;83(1):59-67. (PMID: 7553874)
      J Cell Biol. 2010 May 31;189(5):871-83. (PMID: 20513767)
      J Cell Biol. 2006 Dec 18;175(6):861-8. (PMID: 17178906)
      Trends Cell Biol. 2005 Mar;15(3):146-55. (PMID: 15752978)
      EMBO J. 2001 Jun 15;20(12):3156-66. (PMID: 11406592)
      J Endocrinol. 2008 Feb;196(2):R1-7. (PMID: 18252943)
      J Biol Chem. 2006 Dec 15;281(50):38930-40. (PMID: 17052978)
      Blood. 2008 Sep 15;112(6):2222-31. (PMID: 18487512)
      Cell. 1998 May 1;93(3):397-409. (PMID: 9590174)
      J Biol Chem. 2010 May 7;285(19):14101-8. (PMID: 20189988)
      Mol Oncol. 2009 Aug;3(4):297-307. (PMID: 19615955)
      Trends Endocrinol Metab. 1999 Dec;10(1):18-23. (PMID: 10322390)
      EMBO J. 2003 Oct 15;22(20):5480-90. (PMID: 14532120)
      Blood. 2002 Oct 1;100(7):2279-88. (PMID: 12239135)
      Mol Cell Biol. 2008 Sep;28(17):5275-87. (PMID: 18573876)
      Mol Biol Cell. 2001 Aug;12(8):2556-66. (PMID: 11514635)
      Blood. 2005 Jan 15;105(2):600-8. (PMID: 15358619)
      Blood. 2007 Jun 15;109(12):5215-22. (PMID: 17327410)
      J Biol Chem. 2001 Aug 31;276(35):32635-41. (PMID: 11418602)
      Cell Mol Life Sci. 2003 Oct;60(10):2020-33. (PMID: 14618253)
      Blood. 2010 Feb 11;115(6):1254-63. (PMID: 19880496)
      Curr Biol. 2007 Mar 6;17(5):455-61. (PMID: 17320394)
      Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22. (PMID: 19696798)
      Mol Cell. 2001 Dec;8(6):1327-38. (PMID: 11779507)
      J Immunol. 2000 Dec 1;165(11):6372-80. (PMID: 11086075)
      Mol Cell Biol. 2002 Oct;22(20):7279-90. (PMID: 12242303)
    • Grant Information:
      R01 HL089966 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Receptors, Erythropoietin)
      0 (STAT5 Transcription Factor)
      EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
      EC 3.6.5.2 (ras Proteins)
    • Publication Date:
      Date Created: 20101225 Date Completed: 20110414 Latest Revision: 20211020
    • Publication Date:
      20250114
    • Accession Number:
      PMC3057794
    • Accession Number:
      10.1074/jbc.M110.186890
    • Accession Number:
      21183685