title: Endocytosis and intracellular trafficking of ErbBs.
abstract: This review article describes the pathways and mechanisms of endocytosis and post-endocytic sorting of the EGF receptor (EGFR/ErbB1) and other members of the ErbB family. Growth factor binding to EGFR accelerates its internalization through clathrin-coated pits which is followed by the efficient lysosomal targeting of internalized receptors and results in receptor down-regulation. The role of EGFR interaction with the Grb2 adaptor protein and Cbl ubiquitin ligase, and receptor ubiquitination in the clathrin-dependent internalization and sorting of EGFR in multivesicular endosomes is discussed. Activation and phosphorylation of ErbB2, ErbB3 and ErbB4 also results in their ubiquitination. However, these ErbBs are internalized and targeted to lysosomes less efficiently than EGFR. When overexpressed endocytosis-impaired ErbBs may inhibit the internalization and degradation of EGFR.
authors.affiliation: Department of Pharmacology, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado 80045-0508, USA. alexander.sorkin@uchsc.edu
authors.forename: Alexander
authors.initials: A
authors.lastname: Sorkin
authors.forename: Lai Kuan
authors.initials: LK
authors.lastname: Goh
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018739:Oncogene Proteins v-erbB / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002966:Clathrin; D051380:GRB2 Adaptor Protein; D018739:Oncogene Proteins v-erbB; D020033:Protein Isoforms; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
references.citation: Biophys J. 2003 Aug;85(2):730-43
references.pmid: 12885624
references.citation: Mol Pharmacol. 2006 Nov;70(5):1643-53
references.pmid: 16914641
references.citation: Mech Dev. 2006 Jun;123(6):450-62
references.pmid: 16844358
references.citation: Trends Cell Biol. 2006 Nov;16(11):551-9
references.pmid: 16996268
references.citation: Exp Cell Res. 2003 Mar 10;284(1):78-88
references.pmid: 12648467
references.citation: Methods Enzymol. 1995;257:209-20
references.pmid: 8583923
references.citation: Biochem Soc Trans. 2006 Nov;34(Pt 5):754-6
references.pmid: 17052190
references.citation: Cell. 1989 Oct 6;59(1):33-43
references.pmid: 2790960
references.citation: FASEB J. 2007 Sep;21(11):2849-62
references.pmid: 17463226
references.citation: EMBO J. 2000 Jul 3;19(13):3159-67
references.pmid: 10880430
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4162-7
references.pmid: 18334649
references.citation: Int J Cancer. 2005 Sep 1;116(3):359-67
references.pmid: 15800944
references.citation: Science. 1993 Jul 30;261(5121):612-5
references.pmid: 8342026
references.citation: J Biol Chem. 1995 Jan 13;270(2):619-25
references.pmid: 7822287
references.citation: Traffic. 2007 Nov;8(11):1617-29
references.pmid: 17714434
references.citation: J Cell Biol. 1976 Oct;71(1):159-71
references.pmid: 977646
references.citation: J Biol Chem. 1992 Jan 15;267(2):1129-40
references.pmid: 1309762
references.citation: EMBO Rep. 2005 Oct;6(10):942-8
references.pmid: 16113650
references.citation: Mol Cell. 2001 Feb;7(2):355-65
references.pmid: 11239464
references.citation: Exp Cell Res. 2008 Feb 15;314(4):801-13
references.pmid: 18031739
references.citation: EMBO J. 2006 Jan 11;25(1):1-12
references.pmid: 16052208
references.citation: Genes Dev. 1998 Dec 1;12(23):3663-74
references.pmid: 9851973
references.citation: Cell. 1987 Oct 23;51(2):199-209
references.pmid: 3499230
references.citation: J Cell Sci. 2001 Jun;114(Pt 11):2167-78
references.pmid: 11493652
references.citation: Proc Natl Acad Sci U S A. 1978 Oct;75(10):5025-9
references.pmid: 311005
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12191-6
references.pmid: 12218189
references.citation: J Biol Chem. 1995 Mar 3;270(9):4334-40
references.pmid: 7876195
references.citation: J Biol Chem. 1991 Jun 15;266(17):11083-94
references.pmid: 1645724
references.citation: Mol Cell Biol. 2007 Jul;27(13):5029-39
references.pmid: 17452457
references.citation: Traffic. 2003 Aug;4(8):529-43
references.pmid: 12839496
references.citation: Brain Res Bull. 2007 Jul 12;73(4-6):210-9
references.pmid: 17562386
references.citation: Development. 2004 Nov;131(22):5551-60
references.pmid: 15496447
references.citation: J Cell Biol. 2008 Jan 28;180(2):389-402
references.pmid: 18209100
references.citation: Science. 1990 Feb 23;247(4945):962-4
references.pmid: 2305263
references.citation: J Biol Chem. 1995 Mar 31;270(13):7061-7
references.pmid: 7706244
references.citation: Biochemistry. 1983 Nov 22;22(24):5667-74
references.pmid: 6317024
references.citation: Nat Cell Biol. 2006 Sep;8(9):945-56
references.pmid: 16892055
references.citation: J Biol Chem. 1985 Oct 5;260(22):11944-52
references.pmid: 2995354
references.citation: EMBO J. 1999 Jun 15;18(12):3348-58
references.pmid: 10369675
references.citation: J Biol Chem. 2007 Jan 19;282(3):1658-69
references.pmid: 17121848
references.citation: Curr Opin Cell Biol. 2003 Apr;15(2):143-8
references.pmid: 12648669
references.citation: J Biol Chem. 2006 Oct 27;281(43):32714-23
references.pmid: 16943190
references.citation: J Biol Chem. 1995 Mar 17;270(11):6320-7
references.pmid: 7534311
references.citation: Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37
references.pmid: 11252954
references.citation: Mol Biol Cell. 2008 Jun;19(6):2661-72
references.pmid: 18385515
references.citation: Cell. 1998 Sep 18;94(6):761-71
references.pmid: 9753323
references.citation: J Biol Chem. 2008 May 9;283(19):13233-42
references.pmid: 18319245
references.citation: EMBO Rep. 2007 Jul;8(7):644-50
references.pmid: 17603537
references.citation: Exp Cell Res. 1997 Apr 10;232(1):167-72
references.pmid: 9141633
references.citation: Mol Cell. 2006 Mar 17;21(6):737-48
references.pmid: 16543144
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2760-5
references.pmid: 15701692
references.citation: J Cell Biol. 2003 Aug 4;162(3):435-42
references.pmid: 12900395
references.citation: Cell Res. 2005 Jan;15(1):66-71
references.pmid: 15686631
references.citation: J Cell Biochem. 2006 Aug 15;98(6):1570-83
references.pmid: 16552725
references.citation: J Biol Chem. 1993 Sep 15;268(26):19312-20
references.pmid: 8396132
references.citation: J Cell Biol. 1979 May;81(2):382-95
references.pmid: 313931
references.citation: Mol Cell Biol. 2007 Mar;27(6):2180-8
references.pmid: 17210635
references.citation: Nat Rev Mol Cell Biol. 2002 Aug;3(8):600-14
references.pmid: 12154371
references.citation: Mol Biol Cell. 2007 Sep;18(9):3656-66
references.pmid: 17626164
references.citation: Traffic. 2006 Jun;7(6):686-98
references.pmid: 16683917
references.citation: Nat Cell Biol. 2000 Jul;2(7):407-14
references.pmid: 10878805
references.citation: Curr Biol. 2003 Feb 18;13(4):297-307
references.pmid: 12593795
references.citation: J Cell Physiol. 1984 Sep;120(3):296-302
references.pmid: 6086681
references.citation: Mol Biol Cell. 2000 Nov;11(11):4019-31
references.pmid: 11071924
references.citation: Cancer Res. 2000 Jul 1;60(13):3384-8
references.pmid: 10910043
references.citation: J Cell Biol. 1987 Dec;105(6 Pt 1):2751-62
references.pmid: 2447100
references.citation: J Biol Chem. 2005 Feb 25;280(8):7038-48
references.pmid: 15590694
references.citation: Mol Cell Biol. 2006 Jan;26(2):389-401
references.pmid: 16382132
references.citation: Traffic. 2006 Nov;7(11):1518-27
references.pmid: 16984407
references.citation: J Biol Chem. 2003 Jun 27;278(26):23343-51
references.pmid: 12686539
references.citation: J Cell Biol. 1984 Mar;98(3):1048-53
references.pmid: 6321514
references.citation: Cell. 2006 Mar 10;124(5):897-900
references.pmid: 16530038
references.citation: J Biol Chem. 1997 Mar 28;272(13):8594-601
references.pmid: 9079690
references.citation: EMBO J. 1998 Jun 15;17(12):3385-97
references.pmid: 9628875
references.citation: Mol Biol Cell. 2004 Aug;15(8):3591-604
references.pmid: 15194809
references.citation: Mol Biol Cell. 2007 Mar;18(3):1064-72
references.pmid: 17215517
references.citation: Mol Biol Cell. 2003 Mar;14(3):858-70
references.pmid: 12631709
references.citation: Biofactors. 1989 Mar;2(1):11-5
references.pmid: 2553047
references.citation: J Biol Chem. 2003 Oct 31;278(44):43411-7
references.pmid: 12900408
references.citation: J Cell Sci Suppl. 1985;3:173-86
references.pmid: 3011821
references.citation: EMBO J. 1999 May 4;18(9):2489-99
references.pmid: 10228163
references.citation: EMBO J. 2006 Sep 20;25(18):4195-206
references.pmid: 16932740
references.citation: J Biol Chem. 2001 May 4;276(18):15256-63
references.pmid: 11278603
references.citation: Oncogene. 1996 Mar 7;12(5):1117-25
references.pmid: 8649804
references.citation: Mol Biol Cell. 1999 May;10(5):1621-36
references.pmid: 10233167
references.citation: Science. 1996 Jun 28;272(5270):1935-9
references.pmid: 8658166
references.citation: Trends Cell Biol. 2006 Jun;16(6):317-26
references.pmid: 16716591
references.citation: Mol Biol Cell. 2007 Mar;18(3):732-42
references.pmid: 17182860
references.citation: Trends Biochem Sci. 1992 Jan;17(1):27-32
references.pmid: 1585453
references.citation: J Cell Biol. 1988 Aug;107(2):801-10
references.pmid: 3262110
references.citation: Mol Biol Cell. 2004 Apr;15(4):1557-67
references.pmid: 14742716
references.citation: Mol Cell Biol. 2005 Dec;25(24):11005-18
references.pmid: 16314522
references.citation: J Cell Biol. 1986 Feb;102(2):500-9
references.pmid: 2868013
references.citation: J Cell Biol. 2003 Sep 1;162(5):909-18
references.pmid: 12952941
references.citation: J Biol Chem. 2007 Jul 20;282(29):21278-84
references.pmid: 17545148
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14843-8
references.pmid: 12411582
references.citation: J Biol Chem. 2006 May 5;281(18):12618-24
references.pmid: 16520378
references.citation: J Biol Chem. 2000 Aug 25;275(34):26625-31
references.pmid: 10862618
references.citation: Mol Biol Cell. 2006 Jun;17(6):2513-23
references.pmid: 16554368
references.citation: J Cell Biol. 1995 Apr;129(1):47-54
references.pmid: 7698994
references.citation: Proc Natl Acad Sci U S A. 1984 Apr;81(8):2384-8
references.pmid: 6326124
references.citation: Mol Biol Cell. 1999 Jun;10(6):2087-100
references.pmid: 10359617
references.citation: J Cell Biol. 1983 Aug;97(2):508-21
references.pmid: 6309862
references.citation: Mol Cell. 1999 Dec;4(6):1029-40
references.pmid: 10635327
references.citation: J Cell Biol. 1991 Jan;112(1):55-63
references.pmid: 1986007
references.citation: EMBO J. 2002 Sep 16;21(18):4796-808
references.pmid: 12234920
references.citation: Dev Cell. 2003 Sep;5(3):475-86
references.pmid: 12967566
references.citation: J Cell Biol. 1982 Oct;95(1):73-7
references.pmid: 6128346
references.citation: Oncogene. 1992 Mar;7(3):511-9
references.pmid: 1347917
references.citation: J Cell Biol. 1984 Jun;98(6):2148-59
references.pmid: 6327725
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16904-9
references.pmid: 17940017
references.citation: Traffic. 2008 Jan;9(1):147-55
references.pmid: 17956594
references.citation: Science. 1996 May 17;272(5264):1008-10
references.pmid: 8638121
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32
references.pmid: 15040445
references.citation: J Biol Chem. 1990 Nov 25;265(33):20517-23
references.pmid: 2173710
references.citation: Proc Natl Acad Sci U S A. 1979 Nov;76(11):5689-93
references.pmid: 230489
references.citation: Development. 2008 Jun;135(11):1913-22
references.pmid: 18434417
references.citation: J Cell Sci. 2005 Sep 1;118(Pt 17):3959-71
references.pmid: 16105874
references.citation: EMBO J. 2006 Jun 7;25(11):2347-57
references.pmid: 16688213
references.citation: J Cell Biol. 1979 Oct;83(1):260-5
references.pmid: 315943
references.citation: J Biol Chem. 1990 Sep 15;265(26):15713-23
references.pmid: 1975591
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:277-98
references.pmid: 16689637
references.citation: Mol Cell Biol. 2004 Oct;24(20):8981-93
references.pmid: 15456872
references.citation: Nature. 2002 Mar 14;416(6877):183-7
references.pmid: 11894095
references.citation: Mol Biol Cell. 2007 May;18(5):1683-92
references.pmid: 17332501
references.citation: Nat Methods. 2004 Dec;1(3):209-17
references.pmid: 15782196
references.citation: Cell. 2002 Jan 25;108(2):261-9
references.pmid: 11832215
references.citation: Cancer Cell. 2005 Jun;7(6):575-89
references.pmid: 15950906
references.citation: EMBO J. 1994 Sep 15;13(18):4269-77
references.pmid: 7925272
references.citation: J Biol Chem. 2003 Aug 1;278(31):28950-60
references.pmid: 12754251
references.citation: Biochem J. 2005 Oct 15;391(Pt 2):153-66
references.pmid: 16212556
references.citation: J Biol Chem. 1999 Mar 26;274(13):8865-74
references.pmid: 10085130
references.citation: Nat Cell Biol. 2001 Sep;3(9):802-8
references.pmid: 11533659
references.citation: J Cell Biol. 2002 Apr 1;157(1):91-101
references.pmid: 11916981
references.citation: J Cell Biol. 2004 Aug 16;166(4):487-92
references.pmid: 15314065
references.citation: J Biol Chem. 1991 Dec 5;266(34):23453-60
references.pmid: 1683870
references.citation: Mol Biol Cell. 2004 Dec;15(12):5268-82
references.pmid: 15385631
references.citation: Development. 2008 Jun;135(11):1923-33
references.pmid: 18434418
references.citation: J Biol Chem. 1991 May 5;266(13):8355-62
references.pmid: 2022651
references.citation: J Biol Chem. 2002 Oct 18;277(42):39666-72
references.pmid: 12177062
references.citation: Nat Cell Biol. 2002 Nov;4(11):850-8
references.pmid: 12402043
references.citation: Traffic. 2000 Mar;1(3):248-58
references.pmid: 11208108
references.citation: Oncogene. 1993 Nov;8(11):3021-8
references.pmid: 8105439
references.citation: Curr Opin Cell Biol. 2007 Aug;19(4):436-45
references.pmid: 17662591
references.citation: J Biol Chem. 2007 Oct 19;282(42):30929-37
references.pmid: 17711858
references.citation: Mol Biol Cell. 2005 Mar;16(3):1268-81
references.pmid: 15635092
references.citation: J Cell Sci. 2002 May 1;115(Pt 9):1791-802
references.pmid: 11956311
references.citation: Mol Biol Cell. 2007 Apr;18(4):1312-23
references.pmid: 17287395
references.citation: J Biol Chem. 2006 Aug 25;281(34):24612-22
references.pmid: 16803894
references.citation: Mol Biol Cell. 2008 Aug;19(8):3454-62
references.pmid: 18508924
references.citation: Cancer Res. 2006 Apr 1;66(7):3603-10
references.pmid: 16585185
references.citation: Exp Cell Res. 1988 Mar;175(1):192-205
references.pmid: 2894318
references.citation: J Biol Chem. 2004 Apr 16;279(16):16657-61
references.pmid: 14985334
references.citation: Curr Opin Cell Biol. 1995 Aug;7(4):552-63
references.pmid: 7495576
references.citation: J Biol Chem. 1996 Jun 7;271(23):13377-84
references.pmid: 8662849
references.citation: J Cell Biol. 2002 Mar 4;156(5):843-54
references.pmid: 11864992
references.citation: J Cell Biol. 2008 Mar 24;180(6):1205-18
references.pmid: 18362181
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13332-7
references.pmid: 14597718
references.citation: Biochem Biophys Res Commun. 2007 Mar 9;354(2):505-10
references.pmid: 17250808
references.citation: J Biol Chem. 1998 May 29;273(22):13819-27
references.pmid: 9593726
references.citation: EMBO J. 2004 Aug 18;23(16):3270-81
references.pmid: 15282549
references.citation: J Biol Chem. 1996 Mar 1;271(9):5251-7
references.pmid: 8617810
references.citation: J Biol Chem. 2006 Feb 24;281(8):5094-105
references.pmid: 16371348
references.citation: J Biol Chem. 2002 Jul 26;277(30):27433-41
references.pmid: 12021271
references.citation: J Biol Chem. 2004 Jul 30;279(31):32786-95
references.pmid: 15159412
references.citation: Mol Biol Cell. 2005 Dec;16(12):5832-42
references.pmid: 16207817
references.citation: Mol Biol Cell. 2005 Nov;16(11):5163-74
references.pmid: 16120644
references.citation: Mol Biol Cell. 2002 Apr;13(4):1313-28
references.pmid: 11950941
references.citation: Cell. 1984 Dec;39(2 Pt 1):283-93
references.pmid: 6149810
references.citation: EMBO J. 2006 Dec 13;25(24):5683-92
references.pmid: 17139251