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Annual Review of Biochemistry

Volume 90, 2021

Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis

Abstract

Intricate relationships between endocytosis and cellular signaling, first recognized nearly 40 years ago through the study of tyrosine kinase growth factor receptors, are now known to exist for multiple receptor classes and to affect myriad physiological and developmental processes. This review summarizes our present understanding of how endocytosis orchestrates cellular signaling networks, with an emphasis on mechanistic underpinnings and focusing on two receptor classes—tyrosine kinase and G protein–coupled receptors—that have been investigated in particular detail. Together, these examples provide a useful survey of the current consensus, uncertainties, and controversies in this rapidly advancing area of cell biology.

Keyword(s): downregulation, endocytosis, endosomes, G protein–coupled receptors, receptor tyrosine kinases, signaling
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/content/journals/10.1146/annurev-biochem-081820-092427
2021-06-20
2024-04-25
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Literature Cited

  1. 1. 
    Goh LK, Sorkin A. 2013. Endocytosis of receptor tyrosine kinases. Cold Spring Harb. Perspect. Biol. 5:5a017459
     [Google Scholar]
  2. 2. 
    Sorkin A, von Zastrow M. 2009. Endocytosis and signalling: intertwining molecular networks. Nat. Rev. Mol. Cell Biol. 10:9609–22
     [Google Scholar]
  3. 3. 
    Sigismund S, Confalonieri S, Ciliberto A, Polo S, Scita G, Di Fiore PP. 2012. Endocytosis and signaling: Cell logistics shape the eukaryotic cell plan. Physiol. Rev. 92:1273–366
     [Google Scholar]
  4. 4. 
    Bergeron JJM, Di Guglielmo GM, Dahan S, Dominguez M, Posner BI. 2016. Spatial and temporal regulation of receptor tyrosine kinase activation and intracellular signal transduction. Annu. Rev. Biochem. 85:573–97
     [Google Scholar]
  5. 5. 
    Irannejad R, Tsvetanova NG, Lobingier BT, von Zastrow M 2015. Effects of endocytosis on receptor-mediated signaling. Curr. Opin. Cell Biol. 35:137–43
     [Google Scholar]
  6. 6. 
    Carpenter G, Cohen S. 1976. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J. Cell Biol. 71:1159–71
     [Google Scholar]
  7. 7. 
    Schlessinger J, Shechter Y, Willingham MC, Pastan I. 1978. Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells. PNAS 75:62659–63
     [Google Scholar]
  8. 8. 
    Gorden P, Carpentier JL, Cohen S, Orci L. 1978. Epidermal growth factor: morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. PNAS 75:105025–29
     [Google Scholar]
  9. 9. 
    Sorkin A, Di Fiore PP, Carpenter G. 1993. The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired. Oncogene 8:113021–28
     [Google Scholar]
  10. 10. 
    Baulida J, Kraus MH, Alimandi M, Di Fiore PP, Carpenter G. 1996. All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J. Biol. Chem. 271:95251–57
     [Google Scholar]
  11. 11. 
    Worthylake R, Opresko LK, Wiley HS. 1999. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J. Biol. Chem. 274:138865–74
     [Google Scholar]
  12. 12. 
    Pietilä M, Sahgal P, Peuhu E, Jäntti NZ, Paatero I et al. 2019. SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nat. Commun. 10:12340
     [Google Scholar]
  13. 13. 
    Lund KA, Opresko LK, Starbuck C, Walsh BJ, Wiley HS. 1990. Quantitative analysis of the endocytic system involved in hormone-induced receptor internalization. J. Biol. Chem. 265:2615713–23
     [Google Scholar]
  14. 14. 
    Sigismund S, Woelk T, Puri C, Maspero E, Tacchetti C et al. 2005. Clathrin-independent endocytosis of ubiquitinated cargos. PNAS 102:82760–65
     [Google Scholar]
  15. 15. 
    Fortian A, Dionne LK, Hong SH, Kim W, Gygi SP et al. 2015. Endocytosis of ubiquitylation-deficient EGFR mutants via clathrin-coated pits is mediated by ubiquitylation. Traffic 16:111137–54
     [Google Scholar]
  16. 16. 
    Lill NL, Douillard P, Awwad RA, Ota S, Lupher ML Jr. et al. 2000. The evolutionarily conserved N-terminal region of Cbl is sufficient to enhance down-regulation of the epidermal growth factor receptor. J. Biol. Chem. 275:1367–77
     [Google Scholar]
  17. 17. 
    Levkowitz G, Waterman H, Ettenberg SA, Katz M, Tsygankov AY et al. 1999. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4:61029–40
     [Google Scholar]
  18. 18. 
    Waterman H, Katz M, Rubin C, Shtiegman K, Lavi S et al. 2002. A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling. EMBO J. 21:3303–13
     [Google Scholar]
  19. 19. 
    Choi E, Zhang X, Xing C, Yu H. 2016. Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis. Cell 166:3567–81
     [Google Scholar]
  20. 20. 
    Choi E, Kikuchi S, Gao H, Brodzik K, Nassour I et al. 2019. Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling. Nat. Commun. 10:11473
     [Google Scholar]
  21. 21. 
    Haigler HT, McKanna JA, Cohen S. 1979. Rapid stimulation of pinocytosis in human carcinoma cells A-431 by epidermal growth factor. J. Cell Biol. 83:182–90
     [Google Scholar]
  22. 22. 
    Orth JD, Krueger EW, Weller SG, McNiven MA. 2006. A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization. Cancer Res 66:73603–10
     [Google Scholar]
  23. 23. 
    Boucrot E, Ferreira APA, Almeida-Souza L, Debard S, Vallis Y et al. 2015. Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 517:7535460–65
     [Google Scholar]
  24. 24. 
    Caldieri G, Barbieri E, Nappo G, Raimondi A, Bonora M et al. 2017. Reticulon 3–dependent ER-PM contact sites control EGFR nonclathrin endocytosis. Science 356:6338617–24
     [Google Scholar]
  25. 25. 
    Jastrzębski K, Zdżalik-Bielecka D, Mamińska A, Kalaidzidis Y, Hellberg C, Miaczynska M. 2017. Multiple routes of endocytic internalization of PDGFRβ contribute to PDGF-induced STAT3 signaling. J. Cell Sci. 130:3577–89
     [Google Scholar]
  26. 26. 
    Valdez G, Akmentin W, Philippidou P, Kuruvilla R, Ginty DD, Halegoua S. 2005. Pincher-mediated macroendocytosis underlies retrograde signaling by neurotrophin receptors. J. Neurosci. 25:215236–47
     [Google Scholar]
  27. 27. 
    Vihanto MM. 2006. Caveolin-1 is required for signaling and membrane targeting of EphB1 receptor tyrosine kinase. J. Cell Sci. 119:112299–309
     [Google Scholar]
  28. 28. 
    Pitulescu ME, Adams RH. 2010. Eph/ephrin molecules—a hub for signaling and endocytosis. Genes Dev 24:222480–92
     [Google Scholar]
  29. 29. 
    Kania A, Klein R. 2016. Mechanisms of ephrin-Eph signalling in development, physiology and disease. Nat. Rev. Mol. Cell Biol. 17:4240–56
     [Google Scholar]
  30. 30. 
    Valenzuela JI, Perez F. 2020. Localized intercellular transfer of ephrin-As by trans-endocytosis enables long-term signaling. Dev. Cell 52:1104–17.e5
     [Google Scholar]
  31. 31. 
    Marston DJ, Dickinson S, Nobes CD. 2003. Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion. Nat. Cell Biol. 5:10879–88
     [Google Scholar]
  32. 32. 
    Evergren E, Cobbe N, McMahon HT. 2018. Eps15R and clathrin regulate EphB2-mediated cell repulsion. Traffic 19:144–57
     [Google Scholar]
  33. 33. 
    von Zastrow M, Kobilka BK. 1994. Antagonist-dependent and -independent steps in the mechanism of adrenergic receptor internalization. J. Biol. Chem. 269:2818448–52
     [Google Scholar]
  34. 34. 
    von Zastrow M, Kobilka BK. 1992. Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors. J. Biol. Chem. 267:53530–38
     [Google Scholar]
  35. 35. 
    Goodman OB Jr., Krupnick JG, Santini F, Gurevich VV, Penn RB et al. 1996. β-arrestin acts as a clathrin adaptor in endocytosis of the β2-adrenergic receptor. Nature 383:6599447–50
     [Google Scholar]
  36. 36. 
    Ferguson SS, Downey WE 3rd, Colapietro AM, Barak LS, Ménard L, Caron MG 1996. Role of β-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 271:5247363–66
     [Google Scholar]
  37. 37. 
    Gaidarov I, Krupnick JG, Falck JR, Benovic JL, Keen JH. 1999. Arrestin function in G protein-coupled receptor endocytosis requires phosphoinositide binding. EMBO J. 18:4871–81
     [Google Scholar]
  38. 38. 
    Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SSG et al. 1999. The β2-adrenergic receptor/βarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. PNAS 96:73712–17
     [Google Scholar]
  39. 39. 
    Komolov KE, Benovic JL. 2018. G protein-coupled receptor kinases: past, present and future. Cell Signal 41:17–24
     [Google Scholar]
  40. 40. 
    Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. 1990. β-Arrestin: a protein that regulates β-adrenergic receptor function. Science 248:49621547–50
     [Google Scholar]
  41. 41. 
    Kang Y, Zhou XE, Gao X, He Y, Liu W et al. 2015. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523:7562561–67
     [Google Scholar]
  42. 42. 
    Huang W, Masureel M, Qianhui Q, Janetzko J, Inoue A et al. 2020. Structure of the neurotensin receptor 1 in complex with β-arrestin 1. Nature 579:7798303–8
     [Google Scholar]
  43. 43. 
    Shukla AK, Manglik A, Kruse AC, Xiao K, Reis RI et al. 2013. Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Nature 497:7447137–41
     [Google Scholar]
  44. 44. 
    Liggett SB, Freedman NJ, Schwinn DA, Lefkowitz RJ. 1993. Structural basis for receptor subtype-specific regulation revealed by a chimeric β3/β2-adrenergic receptor. PNAS 90:83665–69
     [Google Scholar]
  45. 45. 
    Eichel K, Jullié D, von Zastrow M 2016. β-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation. Nat. Cell Biol. 18:3303–10
     [Google Scholar]
  46. 46. 
    Liang W, Curran PK, Hoang Q, Moreland RT, Fishman PH. 2004. Differences in endosomal targeting of human β1- and β2-adrenergic receptors following clathrin-mediated endocytosis. J. Cell Sci. 117:5723–34
     [Google Scholar]
  47. 47. 
    Hu LA, Tang Y, Miller WE, Cong M, Lau AG et al. 2000. β1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of β1-adrenergic receptor interaction with N-methyl-d-aspartate receptors. J. Biol. Chem. 275:4938659–66
     [Google Scholar]
  48. 48. 
    Keith DE, Anton B, Murray SR, Zaki PA, Chu PC et al. 1998. μ-Opioid receptor internalization: Opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain. Mol. Pharmacol. 53:3377–84
     [Google Scholar]
  49. 49. 
    Von Zastrow M, Keith DE Jr., Evans CJ 1993. Agonist-induced state of the δ-opioid receptor that discriminates between opioid peptides and opiate alkaloids. Mol. Pharmacol. 44:1166–72
     [Google Scholar]
  50. 50. 
    Just S, Illing S, Trester-Zedlitz M, Lau EK, Kotowski SJ et al. 2013. Differentiation of opioid drug effects by hierarchical multi-site phosphorylation. Mol. Pharmacol. 83:3633–39
     [Google Scholar]
  51. 51. 
    Lau EK, Trester-Zedlitz M, Trinidad JC, Kotowski SJ, Krutchinsky AN et al. 2011. Quantitative encoding of the effect of a partial agonist on individual opioid receptors by multisite phosphorylation and threshold detection. Sci. Signal. 4:185ra52
     [Google Scholar]
  52. 52. 
    Stoeber M, Jullié D, Li J, Chakraborty S, Majumdar S et al. 2020. Agonist-selective recruitment of engineered protein probes and of GRK2 by opioid receptors in living cells. eLife 9:e54208
     [Google Scholar]
  53. 53. 
    Galcheva-Gargova Z, Theroux SJ, Davis RJ. 1995. The epidermal growth factor receptor is covalently linked to ubiquitin. Oncogene 11:122649–55
     [Google Scholar]
  54. 54. 
    Mori S, Heldin CH, Claesson-Welsh L. 1993. Ligand-induced ubiquitination of the platelet-derived growth factor β-receptor plays a negative regulatory role in its mitogenic signaling. J. Biol. Chem. 268:1577–83
     [Google Scholar]
  55. 55. 
    Mori S, Heldin CH, Claesson-Welsh L. 1992. Ligand-induced polyubiquitination of the platelet-derived growth factor β-receptor. J. Biol. Chem. 267:96429–34
     [Google Scholar]
  56. 56. 
    Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. 2003. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol. Cell. Biol. 23:93363–72
     [Google Scholar]
  57. 57. 
    Haugsten EM, Malecki J, Bjørklund SMS, Olsnes S, Wesche J. 2008. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol. Biol. Cell. 19:83390–403
     [Google Scholar]
  58. 58. 
    Valverde P. 2005. Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and downregulation. Biochem. Biophys. Res. Commun. 333:1180–85
     [Google Scholar]
  59. 59. 
    Geetha T, Jiang J, Wooten MW. 2005. Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling. Mol. Cell 20:2301–12
     [Google Scholar]
  60. 60. 
    McKanna JA, Haigler HT, Cohen S. 1979. Hormone receptor topology and dynamics: morphological analysis using ferritin-labeled epidermal growth factor. PNAS 76:115689–93
     [Google Scholar]
  61. 61. 
    Miller K, Beardmore J, Kanety H, Schlessinger J, Hopkins CR. 1986. Localization of the epidermal growth factor (EGF) receptor within the endosome of EGF-stimulated epidermoid carcinoma (A431) cells. J. Cell Biol. 102:2500–9
     [Google Scholar]
  62. 62. 
    Huang F, Zeng X, Kim W, Balasubramani M, Fortian A et al. 2013. Lysine 63-linked polyubiquitination is required for EGF receptor degradation. PNAS 110:3915722–27
     [Google Scholar]
  63. 63. 
    Bell ES, Coelho PP, Ratcliffe CDH, Rajadurai CV, Peschard P et al. 2019. LC3C-mediated autophagy selectively regulates the Met RTK and HGF-stimulated migration and invasion. Cell Rep 29:124053–68.e6
     [Google Scholar]
  64. 64. 
    Sorkin A, Krolenko S, Kudrjavtceva N, Lazebnik J, Teslenko L et al. 1991. Recycling of epidermal growth factor-receptor complexes in A431 cells: identification of dual pathways. J. Cell Biol. 112:155–63
     [Google Scholar]
  65. 65. 
    Grant BD, Donaldson JG. 2009. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 10:9597–608
     [Google Scholar]
  66. 66. 
    Parachoniak CA, Luo Y, Abella JV, Keen JH, Park M. 2011. GGA3 functions as a switch to promote Met receptor recycling, essential for sustained ERK and cell migration. Dev. Cell 20:6751–63
     [Google Scholar]
  67. 67. 
    Pinilla-Macua I, Grassart A, Duvvuri U, Watkins SC, Sorkin A. 2017. EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo. eLife 6:e31993
     [Google Scholar]
  68. 68. 
    Sigismund S, Argenzio E, Tosoni D, Cavallaro E, Polo S, Di Fiore PP. 2008. Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev. Cell 15:2209–19
     [Google Scholar]
  69. 69. 
    Sigismund S, Algisi V, Nappo G, Conte A, Pascolutti R et al. 2013. Threshold-controlled ubiquitination of the EGFR directs receptor fate. EMBO J 32:152140–57
     [Google Scholar]
  70. 70. 
    Hislop JN, von Zastrow M 2011. Role of ubiquitination in endocytic trafficking of G-protein-coupled receptors. Traffic 12:2137–48
     [Google Scholar]
  71. 71. 
    Marchese A, Raiborg C, Santini F, Keen JH, Stenmark H, Benovic JL. 2003. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Dev. Cell 5:5709–22
     [Google Scholar]
  72. 72. 
    Whistler JL, Enquist J, Marley A, Fong J, Gladher F et al. 2002. Modulation of postendocytic sorting of G protein-coupled receptors. Science 297:5581615–20
     [Google Scholar]
  73. 73. 
    He C, Wei Y, Sun K, Li B, Dong X et al. 2013. Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell 154:51085–99
     [Google Scholar]
  74. 74. 
    Dores MR, Lin H, Grimsey NJ, Mendez F, Trejo J. 2015. The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting. Mol. Biol. Cell 26:254660–73
     [Google Scholar]
  75. 75. 
    Dores MR, Chen B, Lin H, Soh UJK, Paing MM et al. 2012. ALIX binds a YPX3L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J. Cell Biol. 197:3407–19
     [Google Scholar]
  76. 76. 
    Sposini S, Jean-Alphonse FG, Ayoub MA, Oqua A, West C et al. 2017. Integration of GPCR signaling and sorting from very early endosomes via opposing APPL1 mechanisms. Cell Rep 21:102855–67
     [Google Scholar]
  77. 77. 
    Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M. 1999. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the β2-adrenergic receptor. Nature 401:6750286–90
     [Google Scholar]
  78. 78. 
    Tanowitz M, von Zastrow M 2003. A novel endocytic recycling signal that distinguishes the membrane trafficking of naturally occurring opioid receptors. J. Biol. Chem. 278:4645978–86
     [Google Scholar]
  79. 79. 
    Lauffer BEL, Melero C, Temkin P, Lei C, Hong W et al. 2010. SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane. J. Cell Biol. 190:4565–74
     [Google Scholar]
  80. 80. 
    Puthenveedu MA, Lauffer B, Temkin P, Vistein R, Carlton P et al. 2010. Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains. Cell 143:5761–73
     [Google Scholar]
  81. 81. 
    Temkin P, Lauffer B, Jäger S, Cimermancic P, Krogan NJ, von Zastrow M 2011. SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat. Cell Biol. 13:6715–21
     [Google Scholar]
  82. 82. 
    Varandas KC, Irannejad R, von Zastrow M 2016. Retromer endosome exit domains serve multiple trafficking destinations and regulate local G protein activation by GPCRs. Curr. Biol. 26:233129–42
     [Google Scholar]
  83. 83. 
    Choy RW-Y, Park M, Temkin P, Herring BE, Marley A et al. 2014. Retromer mediates a discrete route of local membrane delivery to dendrites. Neuron 82:155–62
     [Google Scholar]
  84. 84. 
    Jullié D, Stoeber M, Sibarita J-B, Zieger HL, Bartol TM et al. 2019. A discrete presynaptic vesicle cycle for neuromodulator receptors. Neuron 105:4663–77.e8
     [Google Scholar]
  85. 85. 
    Yudowski GA, Puthenveedu MA, Henry AG, von Zastrow M 2009. Cargo-mediated regulation of a rapid Rab4-dependent recycling pathway. Mol. Biol. Cell 20:112774–84
     [Google Scholar]
  86. 86. 
    Clairfeuille T, Mas C, Chan ASM, Yang Z, Tello-Lafoz M et al. 2016. A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nat. Struct. Mol. Biol. 23:10921–32
     [Google Scholar]
  87. 87. 
    Stoscheck CM, Carpenter G. 1984. Down regulation of epidermal growth factor receptors: direct demonstration of receptor degradation in human fibroblasts. J. Cell Biol. 98:31048–53
     [Google Scholar]
  88. 88. 
    Wells A, Welsh J, Lazar C, Wiley H, Gill G, Rosenfeld M. 1990. Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science 247:4945962–64
     [Google Scholar]
  89. 89. 
    Yoon CH, Lee J, Jongeward GD, Sternberg PW. 1995. Similarity of sli-1, a regulator of vulval development in C. elegans, to the mammalian proto-oncogene c-cbl. Science 269:52271102–5
     [Google Scholar]
  90. 90. 
    Hopper NA, Lee J, Sternberg PW. 2000. ARK-1 inhibits EGFR signaling in C. elegans. Mol. Cell 6:165–75
     [Google Scholar]
  91. 91. 
    Jékely G, Rørth P. 2003. Hrs mediates downregulation of multiple signalling receptors in Drosophila. EMBO Rep 4:121163–68
     [Google Scholar]
  92. 92. 
    Lloyd TE, Atkinson R, Wu MN, Zhou Y, Pennetta G, Bellen HJ. 2002. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 108:2261–69
     [Google Scholar]
  93. 93. 
    Roepstorff K, Grandal MV, Henriksen L, Knudsen SLJ, Lerdrup M et al. 2009. Differential effects of EGFR ligands on endocytic sorting of the receptor. Traffic 10:81115–27
     [Google Scholar]
  94. 94. 
    Reddy CC, French AR, Wiley HS, Wells AS, Lauffenburger DA. 1996. Growth factor/receptor trafficking effects on cell proliferation responses: the EGF system as a paradigm for insight. Cardiovasc. Pathol. 5:5293
     [Google Scholar]
  95. 95. 
    French AR, Sudlow GP, Wiley HS, Lauffenburger DA. 1994. Postendocytic trafficking of epidermal growth factor-receptor complexes is mediated through saturable and specific endosomal interactions. J. Biol. Chem. 269:2215749–55
     [Google Scholar]
  96. 96. 
    Lenferink AEG, Pinkas-Kramarski R, van de Poll ML, van Vugt MJ, Klapper LN et al. 1998. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 17:123385–97
     [Google Scholar]
  97. 97. 
    Wang Z, Zhang L, Yeung TK, Chen X. 1999. Endocytosis deficiency of epidermal growth factor (EGF) receptor-ErbB2 heterodimers in response to EGF stimulation. Mol. Biol. Cell 10:51621–36
     [Google Scholar]
  98. 98. 
    Lanzetti L, Di Fiore PP 2017. Behind the scenes: endo/exocytosis in the acquisition of metastatic traits. Cancer Res 77:81813–17
     [Google Scholar]
  99. 99. 
    Asp N, Kvalvaag A, Sandvig K, Pust S. 2016. Regulation of ErbB2 localization and function in breast cancer cells by ERM proteins. Oncotarget 7:1825443–60
     [Google Scholar]
  100. 100. 
    Pust S, Klokk TI, Musa N, Jenstad M, Risberg B et al. 2013. Flotillins as regulators of ErbB2 levels in breast cancer. Oncogene 32:293443–51
     [Google Scholar]
  101. 101. 
    Gur G, Rubin C, Katz M, Amit I, Citri A et al. 2004. LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J 23:163270–81
     [Google Scholar]
  102. 102. 
    Muratoglu SC, Mikhailenko I, Newton C, Migliorini M, Strickland DK. 2010. Low density lipoprotein receptor-related protein 1 (LRP1) forms a signaling complex with platelet-derived growth factor receptor-β in endosomes and regulates activation of the MAPK pathway. J. Biol. Chem. 285:1914308–17
     [Google Scholar]
  103. 103. 
    Wong ESM, Fong CW, Lim J, Yusoff P, Low BC et al. 2002. Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling. EMBO J 21:184796–808
     [Google Scholar]
  104. 104. 
    Komada M. 2008. Controlling receptor downregulation by ubiquitination and deubiquitination. Curr. Drug Discov. Technol. 5:178–84
     [Google Scholar]
  105. 105. 
    Pareja F, Ferraro DA, Rubin C, Cohen-Dvashi H, Zhang F et al. 2012. Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene 31:434599–608
     [Google Scholar]
  106. 106. 
    Savio MG, Wollscheid N, Cavallaro E, Algisi V, Di Fiore PP et al. 2016. USP9X controls EGFR fate by deubiquitinating the endocytic adaptor Eps15. Curr. Biol. 26:2173–83
     [Google Scholar]
  107. 107. 
    Francavilla C, Papetti M, Rigbolt KTG, Pedersen A-K, Sigurdsson JO et al. 2016. Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. Nat. Struct. Mol. Biol. 23:6608–18
     [Google Scholar]
  108. 108. 
    Xiao G-Y, Schmid SL. 2020. FCHSD2 controls oncogenic ERK1/2 signaling outcome by regulating endocytic trafficking. PLOS Biol 18:7e3000778
     [Google Scholar]
  109. 109. 
    Caswell PT, Chan M, Lindsay AJ, McCaffrey MW, Boettiger D, Norman JC. 2008. Rab-coupling protein coordinates recycling of α5β1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J. Cell Biol. 183:1143–55
     [Google Scholar]
  110. 110. 
    Jo U, Park KH, Whang YM, Sung JS, Won NH et al. 2014. EGFR endocytosis is a novel therapeutic target in lung cancer with wild-type EGFR. Oncotarget 5:51265–78
     [Google Scholar]
  111. 111. 
    Zhang P, Holowatyj AN, Roy T, Pronovost SM, Marchetti M et al. 2019. An SH3PX1-dependent endocytosis-autophagy network restrains intestinal stem cell proliferation by counteracting EGFR-ERK signaling. Dev. Cell 49:4574–89.e5
     [Google Scholar]
  112. 112. 
    Niendorf S, Oksche A, Kisser A, Löhler J, Prinz M et al. 2007. Essential role of ubiquitin-specific protease 8 for receptor tyrosine kinase stability and endocytic trafficking in vivo. Mol. Cell. Biol. 27:135029–39
     [Google Scholar]
  113. 113. 
    Law PY, Hom DS, Loh HH. 1984. Down-regulation of opiate receptor in neuroblastoma × glioma NG108-15 hybrid cells. Chloroquine promotes accumulation of tritiated enkephalin in the lysosomes. J. Biol. Chem. 259:74096–104
     [Google Scholar]
  114. 114. 
    Henry AG, White IJ, Marsh M, von Zastrow M, Hislop JN. 2011. The role of ubiquitination in lysosomal trafficking of δ-opioid receptors. Traffic 12:2170–84
     [Google Scholar]
  115. 115. 
    Haugh JM, Schooler K, Wells A, Wiley HS, Lauffenburger DA. 1999. Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-γ1 signaling pathway. J. Biol. Chem. 274:138958–65
     [Google Scholar]
  116. 116. 
    Haugh JM, Meyer T. 2002. Active EGF receptors have limited access to PtdIns(4,5)P2 in endosomes: implications for phospholipase C and PI 3-kinase signaling. J. Cell Sci. 115:2303–10
     [Google Scholar]
  117. 117. 
    Pinilla-Macua I, Watkins SC, Sorkin A. 2016. Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes. PNAS 113:82122–27
     [Google Scholar]
  118. 118. 
    Ivaska J, Heino J. 2011. Cooperation between integrins and growth factor receptors in signaling and endocytosis. Annu. Rev. Cell Dev. Biol. 27:291–320
     [Google Scholar]
  119. 119. 
    Marquèze-Pouey B, Mailfert S, Rouger V, Goaillard J-M, Marguet D. 2014. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations. PLOS ONE 9:9e106803
     [Google Scholar]
  120. 120. 
    Calebiro D, Sungkaworn T. 2018. Single-molecule imaging of GPCR interactions. Trends Pharmacol. Sci. 39:2109–22
     [Google Scholar]
  121. 121. 
    Harden TK, Cotton CU, Waldo GL, Lutton JK, Perkins JP. 1980. Catecholamine-induced alteration in sedimentation behavior of membrane bound beta-adrenergic receptors. Science 210:4468441–43
     [Google Scholar]
  122. 122. 
    Khan MN, Savoie S, Bergeron JJ, Posner BI. 1986. Characterization of rat liver endosomal fractions. In vivo activation of insulin-stimulable receptor kinase in these structures. J. Biol. Chem. 261:188462–72
     [Google Scholar]
  123. 123. 
    Lai WH, Cameron PH, Doherty JJ, Posner BI, Bergeron JJ. 1989. Ligand-mediated autophosphorylation activity of the epidermal growth factor receptor during internalization. J. Cell Biol. 109:62751–60
     [Google Scholar]
  124. 124. 
    Sorkin A, Von Zastrow M. 2002. Signal transduction and endocytosis: close encounters of many kinds. Nat. Rev. Mol. Cell Biol. 3:8600–14
     [Google Scholar]
  125. 125. 
    Grimes ML, Beattie E, Mobley WC. 1997. A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA. PNAS 94:189909–14
     [Google Scholar]
  126. 126. 
    Riccio A, Pierchala BA, Ciarallo CL, Ginty DD. 1997. An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science 277:53291097–100
     [Google Scholar]
  127. 127. 
    Andres-Alonso M, Ammar MR, Butnaru I, Gomes GM, Acuña Sanhueza G et al. 2019. SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals. Nat. Commun. 10:15448
     [Google Scholar]
  128. 128. 
    Kononenko NL, Claßen GA, Kuijpers M, Puchkov D, Maritzen T et al. 2017. Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. Nat. Commun. 8:114819
     [Google Scholar]
  129. 129. 
    Quinney KB, Frankel EB, Shankar R, Kasberg W, Luong P, Audhya A. 2019. Growth factor stimulation promotes multivesicular endosome biogenesis by prolonging recruitment of the late-acting ESCRT machinery. PNAS 116:146858–67
     [Google Scholar]
  130. 130. 
    Tomas A, Vaughan SO, Burgoyne T, Sorkin A, Hartley JA et al. 2015. WASH and Tsg101/ALIX-dependent diversion of stress-internalized EGFR from the canonical endocytic pathway. Nat. Commun. 6:7324
     [Google Scholar]
  131. 131. 
    Eden ER, White IJ, Tsapara A, Futter CE. 2010. Membrane contacts between endosomes and ER provide sites for PTP1B-epidermal growth factor receptor interaction. Nat. Cell Biol. 12:3267–72
     [Google Scholar]
  132. 132. 
    Li C, Baquiran G, Gu F, Tremblay ML, Fazel A et al. 2006. Insulin receptor kinase-associated phosphotyrosine phosphatases in hepatic endosomes: assessing the role of phosphotyrosine phosphatase-1B. Endocrinology 147:2912–18
     [Google Scholar]
  133. 133. 
    Villaseñor R, Nonaka H, Del Conte-Zerial P, Kalaidzidis Y, Zerial M. 2015. Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes. eLife 4:e06156
     [Google Scholar]
  134. 134. 
    Stanoev A, Mhamane A, Schuermann KC, Grecco HE, Stallaert W et al. 2018. Interdependence between EGFR and phosphatases spatially established by vesicular dynamics generates a growth factor sensing and responding network. Cell Syst 7:3295–309.e11
     [Google Scholar]
  135. 135. 
    Pol A, Calvo M, Enrich C. 1998. Isolated endosomes from quiescent rat liver contain the signal transduction machinery. Differential distribution of activated Raf-1 and Mek in the endocytic compartment. FEBS Lett 441:134–38
     [Google Scholar]
  136. 136. 
    Howe CL, Valletta JS, Rusnak AS, Mobley WC. 2001. NGF signaling from clathrin-coated vesicles: evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway. Neuron 32:5801–14
     [Google Scholar]
  137. 137. 
    Jiang X, Sorkin A. 2002. Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells. Mol. Biol. Cell 13:51522–35
     [Google Scholar]
  138. 138. 
    Surve SV, Myers PJ, Clayton SA, Watkins SC, Lazzara MJ, Sorkin A. 2019. Localization dynamics of endogenous fluorescently labeled RAF1 in EGF-stimulated cells. Mol. Biol. Cell 30:4506–23
     [Google Scholar]
  139. 139. 
    Marshall CJ. 1995. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:2179–85
     [Google Scholar]
  140. 140. 
    Manning BD, Cantley LC. 2007. AKT/PKB signaling: navigating downstream. Cell 129:71261–74
     [Google Scholar]
  141. 141. 
    Saito T, Jones CC, Huang S, Czech MP, Pilch PF. 2007. The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. J. Biol. Chem. 282:4432280–87
     [Google Scholar]
  142. 142. 
    Miaczynska M, Christoforidis S, Giner A, Shevchenko A, Uttenweiler-Joseph S et al. 2004. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 116:3445–56
     [Google Scholar]
  143. 143. 
    Schenck A, Goto-Silva L, Collinet C, Rhinn M, Giner A et al. 2008. The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell 133:3486–97
     [Google Scholar]
  144. 144. 
    Braccini L, Ciraolo E, Campa CC, Perino A, Longo DL et al. 2015. PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling. Nat. Commun. 6:7400
     [Google Scholar]
  145. 145. 
    Schmid SL. 2017. Reciprocal regulation of signaling and endocytosis: implications for the evolving cancer cell. J. Cell Biol. 216:92623–32
     [Google Scholar]
  146. 146. 
    Chen P-H, Bendris N, Hsiao Y-J, Reis CR, Mettlen M et al. 2017. Crosstalk between CLCb/Dyn1-mediated adaptive clathrin-mediated endocytosis and epidermal growth factor receptor signaling increases metastasis. Dev. Cell 40:3278–88.e5
     [Google Scholar]
  147. 147. 
    Reis CR, Chen P-H, Srinivasan S, Aguet F, Mettlen M, Schmid SL. 2015. Crosstalk between Akt/GSK3β signaling and dynamin-1 regulates clathrin-mediated endocytosis. EMBO J 34:162132–46
     [Google Scholar]
  148. 148. 
    Garay C, Judge G, Lucarelli S, Bautista S, Pandey R et al. 2015. Epidermal growth factor-stimulated Akt phosphorylation requires clathrin or ErbB2 but not receptor endocytosis. Mol. Biol. Cell 26:193504–19
     [Google Scholar]
  149. 149. 
    Lucarelli S, Pandey R, Judge G, Antonescu CN. 2016. Similar requirement for clathrin in EGF- and HGF- stimulated Akt phosphorylation. Commun. Integr. Biol. 9:3e1175696
     [Google Scholar]
  150. 150. 
    Palamidessi A, Frittoli E, Garré M, Faretta M, Mione M et al. 2008. Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134:1135–47
     [Google Scholar]
  151. 151. 
    Ménard L, Parker PJ, Kermorgant S. 2014. Receptor tyrosine kinase c-Met controls the cytoskeleton from different endosomes via different pathways. Nat. Commun. 5:3907
     [Google Scholar]
  152. 152. 
    Cosker KE, Segal RA. 2014. Neuronal signaling through endocytosis. Cold Spring Harb. Perspect. Biol. 6:2a020669
     [Google Scholar]
  153. 153. 
    Harrington AW, St Hillaire C, Zweifel LS, Glebova NO, Philippidou P et al. 2011. Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival. Cell 146:3421–34
     [Google Scholar]
  154. 154. 
    Kwok-Keung Fung B, Stryer L. 1980. Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments. PNAS 77:52500–4
     [Google Scholar]
  155. 155. 
    Salinas RY, Pearring JN, Ding J-D, Spencer WJ, Hao Y, Arshavsky VY. 2017. Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release. J. Cell Biol. 216:51489–99
     [Google Scholar]
  156. 156. 
    Pippig S, Andexinger S, Lohse MJ. 1995. Sequestration and recycling of beta 2-adrenergic receptors permit receptor resensitization. Mol. Pharmacol. 47:4666–76
     [Google Scholar]
  157. 157. 
    Krueger KM, Daaka Y, Pitcher JA, Lefkowitz RJ. 1997. The role of sequestration in G protein-coupled receptor resensitization. Regulation of β2-adrenergic receptor dephosphorylation by vesicular acidification. J. Biol. Chem. 272:15–8
     [Google Scholar]
  158. 158. 
    Tsvetanova NG, Irannejad R, von Zastrow M 2015. G protein-coupled receptor (GPCR) signaling via heterotrimeric G proteins from endosomes. J. Biol. Chem. 290:116689–96
     [Google Scholar]
  159. 159. 
    Daaka Y, Luttrell LM, Ahn S, Della Rocca GJ, Ferguson SS et al. 1998. Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J. Biol. Chem. 273:2685–88
     [Google Scholar]
  160. 160. 
    DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. 2007. Beta-arrestins and cell signaling. Annu. Rev. Physiol. 69:483–510
     [Google Scholar]
  161. 161. 
    Slessareva JE, Routt SM, Temple B, Bankaitis VA, Dohlman HG. 2006. Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein α subunit at the endosome. Cell 126:1191–203
     [Google Scholar]
  162. 162. 
    Mullershausen F, Zecri F, Cetin C, Billich A, Guerini D, Seuwen K. 2009. Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat. Chem. Biol. 5:6428–34
     [Google Scholar]
  163. 163. 
    Ferrandon S, Feinstein TN, Castro M, Wang B, Bouley R et al. 2009. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat. Chem. Biol. 5:10734–42
     [Google Scholar]
  164. 164. 
    Calebiro D, Nikolaev VO, Gagliani MC, de Filippis T, Dees C et al. 2009. Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLOS Biol 7:8e1000172
     [Google Scholar]
  165. 165. 
    Kotowski SJ, Hopf FW, Seif T, Bonci A, von Zastrow M. 2011. Endocytosis promotes rapid dopaminergic signaling. Neuron 71:2278–90
     [Google Scholar]
  166. 166. 
    Irannejad R, Tomshine JC, Tomshine JR, Chevalier M, Mahoney JP et al. 2013. Conformational biosensors reveal GPCR signalling from endosomes. Nature 495:7442534–38
     [Google Scholar]
  167. 167. 
    Bowman SL, Shiwarski DJ, Puthenveedu MA. 2016. Distinct G protein-coupled receptor recycling pathways allow spatial control of downstream G protein signaling. J. Cell Biol. 214:7797–806
     [Google Scholar]
  168. 168. 
    Godbole A, Lyga S, Lohse MJ, Calebiro D. 2017. Internalized TSH receptors en route to the TGN induce local Gs-protein signaling and gene transcription. Nat. Commun. 8:1443
     [Google Scholar]
  169. 169. 
    Irannejad R, Pessino V, Mika D, Huang B, Wedegaertner PB et al. 2017. Functional selectivity of GPCR-directed drug action through location bias. Nat. Chem. Biol. 13:7799–806
     [Google Scholar]
  170. 170. 
    Stoeber M, Jullié D, Lobingier BT, Laeremans T, Steyaert J et al. 2018. A genetically encoded biosensor reveals location bias of opioid drug action. Neuron 98:5963–76.e5
     [Google Scholar]
  171. 171. 
    Nash CA, Wei W, Irannejad R, Smrcka AV. 2019. Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy. eLife 8:e48167
     [Google Scholar]
  172. 172. 
    Ramírez-García PD, Retamal JS, Shenoy P, Imlach W, Sykes M et al. 2019. A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prevent chronic pain. Nat. Nanotechnol. 14:121150–59
     [Google Scholar]
  173. 173. 
    Jimenez-Vargas NN, Gong J, Wisdom MJ, Jensen DD, Latorre R et al. 2020. Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain. PNAS 117:2615281–92
     [Google Scholar]
  174. 174. 
    Thomsen ARB, Plouffe B, Cahill TJ 3rd, Shukla AK, Tarrasch JT et al. 2016. GPCR-G protein-β-arrestin super-complex mediates sustained G protein signaling. Cell 166:4907–19
     [Google Scholar]
  175. 175. 
    Lyga S, Volpe S, Werthmann RC, Götz K, Sungkaworn T et al. 2016. Persistent cAMP signaling by internalized LH receptors in ovarian follicles. Endocrinology 157:41613–21
     [Google Scholar]
  176. 176. 
    Ho PWM, Chan AS, Pavlos NJ, Sims NA, Martin TJ. 2019. Brief exposure to full length parathyroid hormone-related protein (PTHrP) causes persistent generation of cyclic AMP through an endocytosis-dependent mechanism. Biochem. Pharmacol. 169:113627
     [Google Scholar]
  177. 177. 
    Wehbi VL, Stevenson HP, Feinstein TN, Calero G, Romero G, Vilardaga J-P. 2013. Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gβγ complex. PNAS 110:41530–35
     [Google Scholar]
  178. 178. 
    Nguyen AH, Thomsen ARB, Cahill TJ 3rd, Huang R, Huang L-Y et al. 2019. Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex. Nat. Struct. Mol. Biol. 26:121123–31
     [Google Scholar]
  179. 179. 
    Clister T, Greenwald EC, Baillie GS, Zhang J. 2019. AKAP95 organizes a nuclear microdomain to control local cAMP for regulating nuclear PKA. Cell Chem. Biol. 26:6885–91.e4
     [Google Scholar]
  180. 180. 
    Tsvetanova NG, von Zastrow M 2014. Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis. Nat. Chem. Biol. 10:121061–65
     [Google Scholar]
  181. 181. 
    O'Banion CP, Vickerman BM, Haar L, Lawrence DS. 2019. Compartmentalized cAMP generation by engineered photoactivated adenylyl cyclases. Cell Chem. Biol. 26:101393–406.e7
     [Google Scholar]
  182. 182. 
    Lazar AM, Irannejad R, Baldwin TA, Sundaram AB, Gutkind JS et al. 2020. G protein-regulated endocytic trafficking of adenylyl cyclase type 9. eLife 9:e58039
     [Google Scholar]
  183. 183. 
    Sunahara RK, Taussig R. 2002. Isoforms of mammalian adenylyl cyclase: multiplicities of signaling. Mol. Interv. 2:3168–84
     [Google Scholar]
  184. 184. 
    Tsvetanova NG, Trester-Zedlitz M, Newton BW, Riordan DP, Sundaram AB et al. 2017. G protein-coupled receptor endocytosis confers uniformity in responses to chemically distinct ligands. Mol. Pharmacol. 91:2145–56
     [Google Scholar]
  185. 185. 
    Teis D, Wunderlich W, Huber LA. 2002. Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction. Dev. Cell 3:6803–14
     [Google Scholar]
  186. 186. 
    Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:2290–303
     [Google Scholar]
  187. 187. 
    Kulak NA, Pichler G, Paron I, Nagaraj N, Mann M. 2014. Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nat. Methods 11:3319–24
     [Google Scholar]
  188. 188. 
    Shi T, Niepel M, McDermott JE, Gao Y, Nicora CD et al. 2016. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway. Sci. Signal. 9:436rs6
     [Google Scholar]
  189. 189. 
    Yang Y-P, Ma H, Starchenko A, Huh WJ, Li W et al. 2017. A chimeric Egfr protein reporter mouse reveals Egfr localization and trafficking in vivo. Cell Rep 19:61257–67
     [Google Scholar]
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Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis
Annual Review of Biochemistry 90, 709 (2021); https://doi.org/10.1146/annurev-biochem-081820-092427
/content/journals/10.1146/annurev-biochem-081820-092427
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