Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction

Annual Review of Biochemistry

Volumn 85, Issue , 2016, Pages 573-597

  Bergeron, John J M ^a   Di Guglielmo, Gianni M ^b   Dahan, Sophie ^a   Dominguez, Michel ^a   Posner, Barry I ^a  

^a MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

EGF; Insulin; Ligand degradation; Membrane trafficking; Signaling endosome; Signaling interactome

Indexed keywords

ENDOPHILIN; EPIDERMAL GROWTH FACTOR; G PROTEIN COUPLED RECEPTOR; INSULIN; LIGAND; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; EGFR PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR RECEPTOR; INSULIN RECEPTOR TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE;

ARTICLE; AUTOPHAGOSOME; AUTOPHOSPHORYLATION; CELL FUSION; CELL MATURATION; CELL MEMBRANE; CELL MIGRATION; CELL ORGANELLE; CELL PROLIFERATION; CLATHRIN-COATED VESICLE; DOWN REGULATION; ENDOCYTOSIS; ENDOSOME; ENZYME ACTIVATION; ENZYME DEGRADATION; ENZYME REGULATION; EXOSOME; HUMAN; INTERACTOME; INTERNALIZATION; INTRACELLULAR SIGNALING; LIVER; LYSOSOME; MEMBRANE FUSION; NONHUMAN; PINOCYTOSIS; PRIORITY JOURNAL; GENE EXPRESSION REGULATION; GENETICS; INTRACELLULAR MEMBRANE; METABOLISM; PHOSPHORYLATION; PHYSIOLOGICAL FEEDBACK; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION;

CELL MEMBRANE; ENDOCYTOSIS; ENDOSOMES; EPIDERMAL GROWTH FACTOR; FEEDBACK, PHYSIOLOGICAL; GENE EXPRESSION REGULATION; HUMANS; INSULIN; INTRACELLULAR MEMBRANES; PHOSPHORYLATION; PROTEIN TRANSPORT; PROTEIN TYROSINE PHOSPHATASES; PROTEIN-TYROSINE KINASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84974716090     PISSN: 00664154     EISSN: 15454509     Source Type: Book Series    
DOI: 10.1146/annurev-biochem-060815-014659     Document Type: Article

References (146)

1. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, et al. 2000. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell 6:87-97
2. Kadowaki T, Kubota N, Ueki K, Yamauchi T. 2012. SnapShot: physiology of insulin signaling. Cell 148:834-834. E1
3. Boucher J, Kleinridders A, Kahn CR. 2014. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol. 6:a009191
4. Kang LI, MarsWM, Michalopoulos GK. 2012. Signals and cells involved in regulating liver regeneration. Cells 1:1261-92
5. Natarajan A, Wagner B, Sibilia M. 2007. The EGF receptor is required for efficient liver regeneration. PNAS 104:17081-86
6. Yarden Y, Shilo BZ. 2007. SnapShot: EGFR signaling pathway. Cell 131:1018
7. Bergeron JJ, Levine G, Sikstrom R, O'Shaughnessy D, Kopriwa B, et al. 1977. Polypeptide hormone binding sites in vivo: initial localization of 125I-labeled insulin to hepatocyte plasmalemma as visualized by electron microscope radioautography. PNAS 74:5051-55
8. Bergeron JJ, Sikstrom R, Hand AR, Posner BI. 1979. Binding and uptake of 125I-insulin into rat liver hepatocytes and endothelium. An in vivo radioautographic study. J. Cell Biol. 80:427-43
9. KhanMN, Posner BI, Khan RJ, Bergeron JJ. 1982. Internalization of insulin into rat liver Golgi elements. Evidence for vesicle heterogeneity and the path of intracellular processing. J. Biol. Chem. 257:5969-76
10. Posner BI, Patel B, Verma AK, Bergeron JJ. 1980. Uptake of insulin by plasmalemma and Golgi subcellular fractions of rat liver. J. Biol. Chem. 255:735-41
11. Dahan S, Ahluwalia JP, Wong L, Posner BI, Bergeron JJ. 1994. Concentration of intracellular hepatic apolipoprotein E in Golgi apparatus saccular distensions and endosomes. J. Cell Biol. 127:1859-69
12. 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. 261:8462-72
13. Posner BI, Faure R, Burgess JW, Bevan AP, Lachance D, et al. 1994. Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. J. Biol. Chem. 269:4596-604
14. Bevan AP, Burgess JW, Drake PG, Shaver A, Bergeron JJ, Posner BI. 1995. Selective activation of the rat hepatic endosomal insulin receptor kinase. Role for the endosome in insulin signaling. J. Biol. Chem. 270:10784-91
15. Carpentier JL, Gorden P, Anderson RG, Goldstein JL, Brown MS, et al. 1982. Co-localization of 125I-epidermal growth factor and ferritin-low density lipoprotein in coated pits: A quantitative electron microscopic study in normal and mutant human fibroblasts. J. Cell Biol. 95:73-77
16. Cohen S, Fava RA. 1985. Internalization of functional epidermal growth factor:receptor/kinase complexes in A-431 cells. J. Biol. Chem. 260:12351-58
17. Dunn WA, Connolly TP, Hubbard AL. 1986. Receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes: receptor pathway. J. Cell Biol. 102:24-36
18. Dunn WA, Hubbard AL. 1984. Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics. J. Cell Biol. 98:2148-59
19. Fortian A, Sorkin A. 2014. Live-cell fluorescence imaging reveals high stoichiometry of Grb2 binding to the EGF receptor sustained during endocytosis. J. Cell Sci. 127:432-44
20. Haigler HT, McKanna JA, Cohen S. 1979. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J. Cell Biol. 81:382-95
21. 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. 102:500-9
22. Di Guglielmo GM, Baass PC, Ou WJ, Posner BI, Bergeron JJ. 1994. Compartmentalization of SHC, GRB2 and mSOS, and hyperphosphorylation of Raf-1 by EGF but not insulin in liver parenchyma. EMBO J. 13:4269-77
23. Kay DG, Lai WH, Uchihashi M, Khan MN, Posner BI, Bergeron JJ. 1986. Epidermal growth factor receptor kinase translocation and activation in vivo. J. Biol. Chem. 261:8473-80
24. LaiWH, Cameron PH, Doherty JJ 2nd, Posner BI, Bergeron JJ. 1989. Ligand-mediated autophosphorylation activity of the epidermal growth factor receptor during internalization. J. Cell Biol. 109:2751-60
25. LaiWH, Cameron PH, Wada I, Doherty JJ 2nd, Kay DG, et al. 1989. Ligand-mediated internalization, recycling, and downregulation of the epidermal growth factor receptor in vivo. J. Cell Biol. 109:2741-49
26. Wada I, Lai WH, Posner BI, Bergeron JJ. 1992. Association of the tyrosine phosphorylated epidermal growth factor receptor with a 55-kD tyrosine phosphorylated protein at the cell surface and in endosomes. J. Cell Biol. 116:321-30
27. Authier F, Di Guglielmo GM, Danielsen GM, Bergeron JJ. 1998. Uptake and metabolic fate of [HisA8, HisB4, GluB10, HisB27]insulin in rat liver in vivo. Biochem. J. 332(Pt. 2):421-30
28. Authier F, Metioui M, Bell AW, Mort JS. 1999. Negative regulation of epidermal growth factor signaling by selective proteolytic mechanisms in the endosomemediated by cathepsin B. J. Biol. Chem. 274:33723-31
29. Authier F, Metioui M, Fabrega S, Kouach M, Briand G. 2002. Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D. J. Biol. Chem. 277:9437-46
30. Authier F, Rachubinski RA, Posner BI, Bergeron JJ. 1994. Endosomal proteolysis of insulin by an acidic thiol metalloprotease unrelated to insulin degrading enzyme. J. Biol. Chem. 269:3010-16
31. Hamel FG, Posner BI, Bergeron JJ, Frank BH, DuckworthWC. 1988. Isolation of insulin degradation products from endosomes derived from intact rat liver. J. Biol. Chem. 263:6703-8
32. Villaseñor R, NonakaH, Del Conte-Zerial P, Kalaidzidis Y, Zerial M. 2015. Regulation of EGFR signal transduction by analogue-to-digital conversion in endosomes. ELife 4:e06156
33. Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I. 2010. Spatial control of EGF receptor activation by reversible dimerization on living cells. Nature 464:783-87
34. WileyHS, Cunningham DD. 1982. The endocytotic rate constant. A cellular parameter for quantitating receptor-mediated endocytosis. J. Biol. Chem. 257:4222-29
35. Hofman EG, Bader AN, Voortman J, van den Heuvel DJ, Sigismund S, et al. 2010. Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization. J. Biol. Chem. 285:39481-89
36. Wiley HS, Cunningham DD. 1981. A steady state model for analyzing the cellular binding, internalization and degradation of polypeptide ligands. Cell 25:433-40
37. Bitsikas V, Correa IRJr, NicholsBJ. 2014. Clathrin-independent pathways do not contribute significantly to endocytic flux. ELife 3:e03970
38. Rappoport JZ, Simon SM. 2009. Endocytic trafficking of activated EGFR is AP-2 dependent and occurs through preformed clathrin spots. J. Cell Sci. 122:1301-5
39. Jura N, Endres NF, Engel K, Deindl S, Das R, et al. 2009. Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell 137:1293-307
40. Goh LK, Huang F, Kim W, Gygi S, Sorkin A. 2010. Multiple mechanisms collectively regulate clathrinmediated endocytosis of the epidermal growth factor receptor. J. Cell Biol. 189:871-83
41. Huang F, Jiang X, Sorkin A. 2003. Tyrosine phosphorylation of the ?2 subunit of clathrin adaptor complex AP-2 reveals the role of a di-leucine motif in the epidermal growth factor receptor trafficking. J. Biol. Chem. 278:43411-17
42. Taylor MJ, Lampe M, Merrifield CJ. 2012. A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis. PLOS Biol. 10:e1001302
43. Taylor MJ, Perrais D, Merrifield CJ. 2011. A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLOS Biol. 9:e1000604
44. Wang Z, Moran MF. 1996. Requirement for the adapter protein GRB2 in EGF receptor endocytosis. Science 272:1935-39
45. Sousa LP, Lax I, Shen H, Ferguson SM, De Camilli P, Schlessinger J. 2012. Suppression of EGFR endocytosis by dynamin depletion reveals thatEGFRsignaling occurs primarily at the plasma membrane. PNAS 109:4419-24
46. Schmees C, Villaseñor R, Zheng W, Ma H, Zerial M, et al. 2012. Macropinocytosis of the PDGF receptor promotes fibroblast transformation by H-RasG12V. Mol. Biol. Cell 23:2571-82
47. Boucrot E, Ferreira AP, Almeida-Souza L, Debard S, Vallis Y, et al. 2015. Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 517:460-65
48. Renard HF, Simunovic M, Lemiere J, Boucrot E, Garcia-Castillo MD, et al. 2015. Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis. Nature 517:493-96
49. Foret L, Dawson JE, Villaseñor R, Collinet C, Deutsch A, et al. 2012. A general theoretical framework to infer endosomal network dynamics from quantitative image analysis. Curr. Biol. 22:1381-90
50. Rink J, Ghigo E, Kalaidzidis Y, Zerial M. 2005. Rab conversion as a mechanism of progression from early to late endosomes. Cell 122:735-49
51. Cavalli V, Vilbois F, Corti M, MarcoteMJ, Tamura K, et al. 2001. The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex. Mol. Cell 7:421-32
52. Mace G, Miaczynska M, Zerial M, Nebreda AR. 2005. Phosphorylation of EEA1 by p38 MAP kinase regulates mu opioid receptor endocytosis. EMBO J. 24:3235-46
53. Lim B, Dsilva CJ, Levario TJ, Lu H, Schupbach T, et al. 2015. Dynamics of inductive ERK signaling in the Drosophila embryo. Curr. Biol. 25:1784-90
54. 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 147:912-18
55. Naguib A, Bencze G, Cho H, Zheng W, Tocilj A, et al. 2015. PTEN functions by recruitment to cytoplasmic vesicles. Mol. Cell 58:255-68
56. Albeck JG, Mills GB, Brugge JS. 2013. Frequency-modulated pulses ofERKactivity transmit quantitative proliferation signals. Mol. Cell 49:249-61
57. Raiborg C, Wenzel EM, Stenmark H. 2015. ER-endosome contact sites: molecular compositions and functions. EMBO J. 34:1848-58
58. Rowland AA, Chitwood PJ, Phillips MJ, Voeltz GK. 2014. ER contact sites define the position and timing of endosome fission. Cell 159:1027-41
59. Raiborg C, Wenzel EM, Pedersen NM, Olsvik H, Schink KO, et al. 2015. Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth. Nature 520:234-38
60. Haj FG, Verveer PJ, Squire A, Neel BG, Bastiaens PI. 2002. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 295:1708-11
61. Yudushkin IA, Schleifenbaum A, Kinkhabwala A, Neel BG, Schultz C, Bastiaens PI. 2007. Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B. Science 315:115-19
62. Steinman RM, Brodie SE, Cohn ZA. 1976. Membrane flow during pinocytosis. A stereologic analysis. J. Cell Biol. 68:665-87
63. Steinman RM, Mellman IS, Muller WA, Cohn ZA. 1983. Endocytosis and the recycling of plasma membrane. J. Cell Biol. 96:1-27
64. Doherty JJ 2nd, Kay DG, LaiWH, Posner BI, Bergeron JJ. 1990. Selective degradation of insulin within rat liver endosomes. J. Cell Biol. 110:35-42
65. Diment S, LeechMS, Stahl PD. 1988. Cathepsin D is membrane-associated in macrophage endosomes. J. Biol. Chem. 263:6901-7
66. Diment S, Stahl P. 1985. Macrophage endosomes contain proteases which degrade endocytosed protein ligands. J. Biol. Chem. 260:15311-17
67. Brankatschk B, Wichert SP, Johnson SD, Schaad O, Rossner MJ, Gruenberg J. 2012. Regulation of the EGF transcriptional response by endocytic sorting. Sci. Signal 5:ra21
68. Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M. 2003. A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nat. Biotechnol. 21:315-18
69. Bennett AM, Hausdorff SF, O'Reilly AM, Freeman RM, Neel BG. 1996. Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression. Mol. Cell. Biol. 16:1189-202
70. Schulze WX, Deng L, MannM. 2005. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol. Syst. Biol. 1:2005. 0008
71. Zheng Y, Zhang C, Croucher DR, Soliman MA, St-Denis N, et al. 2013. Temporal regulation of EGF signalling networks by the scaffold protein Shc1. Nature 499:166-71
72. Tong J, Taylor P, MoranMF. 2014. Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress. Mol. Cell. Proteomics 13:1644-58
73. Haines E, Saucier C, Claing A. 2014. The adaptor proteins p66Shc and Grb2 regulate the activation of the GTPases ARF1 and ARF6 in invasive breast cancer cells. J. Biol. Chem. 289:5687-703
74. Argenzio E, Bange T, Oldrini B, Bianchi F, Peesari R, et al. 2011. Proteomic snapshot of the EGFinduced ubiquitin network. Mol. Syst. Biol. 7:462-76
75. Kazazic M, Bertelsen V, Pedersen KW, Vuong TT, Grandal MV, et al. 2009. Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits. Traffic 10:235-45
76. Zhang Z, Zhang T, Wang S, Gong Z, Tang C, et al. 2014. Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5. ELife 3:e02687
77. Selbach M, Mann M. 2006. Protein interaction screening by quantitative immunoprecipitation combined with knockdown (QUICK). Nat. Methods 3:981-83
78. Balbis A, BaquiranG, Bergeron JJ, Posner BI. 2000. Compartmentalization and insulin-induced translocations of insulin receptor substrates, phosphatidylinositol 3-kinase, and protein kinase B in rat liver. Endocrinology 141:4041-49
79. Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, et al. 2000. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J. Clin. Investig. 105:199-205
80. Braccini L, Ciraolo E, Campa CC, Perino A, Longo DL, et al. 2015. PI3K-C2gamma is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling. Nat. Commun. 6:7400
81. CarusoM, MaD, Msallaty Z, Lewis M, Seyoum B, et al. 2014. Increased interaction with insulin receptor substrate 1, a novel abnormality in insulin resistance and type 2 diabetes. Diabetes 63:1933-47
82. Schmelzle K, Kane S, Gridley S, Lienhard GE, White FM. 2006. Temporal dynamics of tyrosine phosphorylation in insulin signaling. Diabetes 55:2171-79
83. Kruger M, Kratchmarova I, Blagoev B, Tseng YH, Kahn CR, Mann M. 2008. Dissection of the insulin signaling pathway via quantitative phosphoproteomics. PNAS 105:2451-56
84. Zeigerer A, Bogorad RL, Sharma K, Gilleron J, Seifert S, et al. 2015. Regulation of liver metabolism by the endosomal GTPase Rab5. Cell Rep. 11:884-92
85. Pan BT, Johnstone RM. 1983. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33:967-78
86. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, et al. 2008. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10:619-24
87. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, InanlouMR, et al. 2012. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151:1542-56
88. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, et al. 2012. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18:883-91
89. Bissig C, Gruenberg J. 2014. ALIX and the multivesicular endosome: ALIX in Wonderland. Trends Cell Biol. 24:19-25
90. Zomer A, Maynard C, Verweij FJ, Kamermans A, Schafer R, et al. 2015. In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 161:1046-57
91. RenfrewCA, Hubbard AL. 1991. Degradation of epidermal growth factor receptor in rat liver. Membrane topology through the lysosomal pathway. J. Biol. Chem. 266:21265-73
92. Gireud M, SirisaengtaksinN, Tsunoda S, Bean AJ. 2015. Cell-free reconstitution of multivesicular body (MVB) cargo sorting. Methods Mol. Biol. 1270:115-24
93. VogelGF, EbnerHL, de Araujo ME, SchmiedingerT, Eiter O, et al. 2015. Ultrastructuralmorphometry points to a new role for LAMTOR2 in regulating the endo/lysosomal system. Traffic 16:617-34
94. Zhang A, He X, Zhang L, Yang L, Woodman P, Li W. 2014. Biogenesis of lysosome-related organelles complex-1 subunit 1 (BLOS1) interacts with sorting nexin 2 and the endosomal sorting complex required for transport-I (ESCRT-I) component TSG101 to mediate the sorting of epidermal growth factor receptor into endosomal compartments. J. Biol. Chem. 289:29180-94
95. Ploper D, De Robertis EM. 2015. The MITF family of transcription factors: role in endolysosomal biogenesis, Wnt signaling, and oncogenesis. Pharmacol. Res. 99:36-43
96. Ploper D, Taelman VF, Robert L, Perez BS, Titz B, et al. 2015. MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells. PNAS 112:E420-29
97. Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC, Vorwald PP, et al. 2010. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143:1136-48
98. Reis CR, Chen PH, Srinivasan S, Aguet F, Mettlen M, Schmid SL. 2015. Crosstalk between Akt/GSK3? signaling and dynamin-1 regulates clathrin-mediated endocytosis. EMBO J. 34:2111-210
99. Marshall S. 1985. Kinetics of insulin receptor internalization and recycling in adipocytes. Shunting of receptors to a degradative pathway by inhibitors of recycling. J. Biol. Chem. 260:4136-44
100. Marshall S, Green A, Olefsky JM. 1981. Evidence for recycling of insulin receptors in isolated rat adipocytes. J. Biol. Chem. 256:11464-70
101. Marshall S, Olefsky JM. 1983. Separate intracellular pathways for insulin receptor recycling and insulin degradation in isolated rat adipocytes. J. Cell Physiol. 117:195-203
102. Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, et al. 2015. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347:188-94
103. Bar-Peled L, Sabatini DM. 2014. Regulation of mTORC1 by amino acids. Trends Cell Biol. 24:400-6
104. Xu Y, Parmar A, Roux E, Balbis A, Dumas V, et al. 2012. Epidermal growth factor-induced vacuolar (H+)-ATPase assembly: A role in signaling via mTORC1 activation. J. Biol. Chem. 287:26409-22
105. Soliman MA, Abdel Rahman AM, Lamming DW, Birsoy K, Pawling J, et al. 2014. The adaptor protein p66Shc inhibits mTOR-dependent anabolic metabolism. Sci. Signal 7:ra17
106. Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. 2003. Distinct endocytic pathways regulate TGF-?receptor signalling and turnover. Nat. Cell Biol. 5:410-21
107. Hayes S, Chawla A, Corvera S. 2002. TGF?receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J. Cell Biol. 158:1239-49
108. Itoh F, Divecha N, Brocks L, Oomen L, Janssen H, et al. 2002. The FYVE domain in Smad anchor for receptor activation (SARA) is sufficient for localization of SARA in early endosomes and regulates TGF-?/Smad signalling. Genes Cells 7:321-31
109. Panopoulou E, Gillooly DJ, Wrana JL, Zerial M, Stenmark H, et al. 2002. Early endosomal regulation of Smad-dependent signaling in endothelial cells. J. Biol. Chem. 277:18046-52
110. Runyan CE, SchnaperHW, Poncelet AC. 2005. The role of internalization in transforming growth factor ?1-induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2-dependent signaling in human mesangial cells. J. Biol. Chem. 280:8300-8
111. Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL. 1998. SARA, a FYVE domain protein that recruits Smad2 to the TGF?receptor. Cell 95:779-91
112. Schwartz EA, Reaven E, Topper JN, Tsao PS. 2005. Transforming growth factor-?receptors localize to caveolae and regulate endothelial nitric oxide synthase in normal human endothelial cells. Biochem. J. 390:199-206
113. Zhang XL, Topley N, Ito T, Phillips A. 2005. Interleukin-6 regulation of transforming growth factor (TGF)-? receptor compartmentalization and turnover enhances TGF-?1 signaling. J. Biol. Chem. 280:12239-45
114. Zwaagstra JC, Collins C, Langlois MJ, O'Connor-McCourt MD. 2008. Analysis of the contribution of receptor subdomains to the cooperative binding and internalization of transforming growth factor-? (TGF-?) type I and type II receptors. Exp. Cell Res. 314:2553-68
115. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, et al. 2001. Smurf1 interacts with transforming growth factor-? type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276:12477-80
116. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, et al. 2000. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF?receptor for degradation. Mol. Cell 6:1365-75
117. Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, et al. 2005. Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Mol. Cell 19:297-308
118. Duan X, Liang YY, Feng XH, Lin X. 2006. Protein serine/threonine phosphatase PPM1A dephosphorylates Smad1 in the bone morphogenetic protein signaling pathway. J. Biol. Chem. 281:36526-32
119. Lin X, Duan X, Liang YY, Su Y, Wrighton KH, et al. 2006. PPM1A functions as a Smad phosphatase to terminate TGF?signaling. Cell 125:915-28
120. Ito T, Williams JD, Fraser DJ, Phillips AO. 2004. Hyaluronan regulates transforming growth factor-?1 receptor compartmentalization. J. Biol. Chem. 279:25326-32
121. Ehrlich M, Shmuely A, Henis YI. 2001. A single internalization signal from the di-leucine family is critical for constitutive endocytosis of the type II TGF-?receptor. J. Cell Sci. 114:1777-86
122. YaoD, Ehrlich M, Henis YI, Leof EB. 2002. Transforming growth factor-?receptors interact with AP2 by direct binding to ?2 subunit. Mol. Biol. Cell 13:4001-12
123. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP. 1997. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J. Biol. Chem. 272:6525-33
124. Razani B, Zhang XL, BitzerM, von Gersdorff G, Bottinger EP, Lisanti MP. 2001. Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. J. Biol. Chem. 276:6727-38
125. He K, Yan X, Li N, Dang S, Xu L, et al. 2015. Internalization of the TGF-? type I receptor into caveolin-1 and EEA1 double-positive early endosomes. Cell Res. 25:738-52
126. Zerial M, McBride H. 2001. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2:107-17
127. Luttrell LM. 2008. Reviews in molecular biology and biotechnology: Transmembrane signaling by G protein-coupled receptors. Mol. Biotechnol. 39:239-64
128. Neer EJ. 1995. Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80:249-57
129. Ferrandon S, Feinstein TN, CastroM, Wang B, Bouley R, et al. 2009. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat. Chem. Biol. 5:734-42
130. LohseMJ, Nuber S, Hoffmann C. 2012. Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol. Rev. 64:299-336
131. Vilardaga JP, BunemannM, Feinstein TN, Lambert N, NikolaevVO, et al. 2009. GPCRandGproteins: drug efficacy and activation in live cells. Mol. Endocrinol. 23:590-99
132. 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:e1000172
133. 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. 5:428-34
134. Kuna RS, Girada SB, Asalla S, Vallentyne J, Maddika S, et al. 2013. Glucagon-like peptide-1 receptormediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic cells. Am. J. Physiol. Endocrinol. Metab. 305:E161-70
135. Merriam LA, BaranCN, Girard BM, Hardwick JC, May V, ParsonsRL. 2013. Pituitary adenylate cyclase 1 receptor internalization and endosomal signaling mediate the pituitary adenylate cyclase activating polypeptide-induced increase in guinea pig cardiac neuron excitability. J. Neurosci. 33:4614-22
136. Feinstein TN, Yui N, Webber MJ, Wehbi VL, Stevenson HP, et al. 2013. Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin. J. Biol. Chem. 288:27849-60
137. Luttrell LM, Gesty-Palmer D. 2010. Beyond desensitization: physiological relevance of arrestindependent signaling. Pharmacol. Rev. 62:305-30
138. Sorkin A, von Zastrow M. 2009. Endocytosis and signalling: intertwining molecular networks. Nat. Rev. Mol. Cell Biol. 10:609-22
139. Rosciglione S, Theriault C, Boily MO, Paquette M, Lavoie C. 2014. G?s regulates the post-endocytic sorting of G protein-coupled receptors. Nat. Commun. 5:4556
140. Vieira AV, Lamaze C, Schmid SL. 1996. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274:2086-89
141. Wang Y, Pennock S, Chen X, Wang Z. 2002. Endosomal signaling of epidermal growth factor receptor stimulates signal transduction pathways leading to cell survival. Mol. Cell. Biol. 22:7279-90
142. Irannejad R, Tsvetanova NG, Lobingier BT, von Zastrow M. 2015. Effects of endocytosis on receptormediated signaling. Curr. Opin. Cell Biol. 35:137-43
143. Miaczynska M. 2013. Effects of membrane trafficking on signaling by receptor tyrosine kinases. Cold Spring Harb. Perspect. Biol. 5:a009035
144. Kruger J, Brachs S, Trappiel M, Kintscher U, Meyborg H, et al. 2015. Enhanced insulin signaling in density-enhanced phosphatase-1 (DEP-1) knockout mice. Mol. Metab. 4:325-36
145. Liberali P, Snijder B, Pelkmans L. 2014. A hierarchical map of regulatory genetic interactions in membrane trafficking. Cell 157:1473-87
146. Noda NN, Fujioka Y. 2015. Atg1 family kinases in autophagy initiation. Cell. Mol. Life Sci. 72:3083-96