EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics

Cell

Volumn 171, Issue 3, 2017, Pages 683-695.e18

  Freed, Daniel M ^a,b   Bessman, Nicholas J ^c   Kiyatkin, Anatoly ^a,b   Salazar Cavazos, Emanuel ^d   Byrne, Patrick O ^e   Moore, Jason O ^c   Valley, Christopher C ^d   Ferguson, Kathryn M ^a,b   Leahy, Daniel J ^e   Lidke, Diane S ^d   Lemmon, Mark A ^a,b,c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b YALE UNIVERSITY   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER   (United States)

^e UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

biased agonist; cell fate decision; crystallography; dimerization; growth factor; kinetic proofreading; negative feedback; phosphatase; receptor tyrosine kinase; signaling specificity

Indexed keywords

EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIGEN; EPIREGULIN; G PROTEIN COUPLED RECEPTOR; PROTEIN TYROSINE KINASE; EGFR PROTEIN, HUMAN; EPGN PROTEIN, HUMAN; EREG PROTEIN, HUMAN; LIGAND;

ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CRYSTALLOGRAPHY; DIMERIZATION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN STABILITY; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SK-BR-3 CELL LINE; T-47D CELL LINE; CHEMISTRY; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN; KINETICS; METABOLISM; MOLECULAR MODEL; PROTEIN MULTIMERIZATION; X RAY CRYSTALLOGRAPHY;

CRYSTALLOGRAPHY, X-RAY; EPIGEN; EPIREGULIN; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMANS; KINETICS; LIGANDS; MODELS, MOLECULAR; PROTEIN MULTIMERIZATION; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 85030626124     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2017.09.017     Document Type: Article

References (68)

1. Adams, P.D., Afonine, P.V., Bunkóczi, G., Chen, V.B., Davis, I.W., Echols, N., Headd, J.J., Hung, L.W., Kapral, G.J., Grosse-Kunstleve, R.W., et al. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66 (2010), 213–221.
2. Aksamitiene, E., Hoek, J.B., Kiyatkin, A., Multistrip western blotting: A tool for comparative quantitative analysis of multiple proteins. Methods Mol. Biol. 1312 (2015), 197–226.
3. Alvarado, D., Klein, D.E., Lemmon, M.A., ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor. Nature 461 (2009), 287–291.
4. Alvarado, D., Klein, D.E., Lemmon, M.A., Structural basis for negative cooperativity in growth factor binding to an EGF receptor. Cell 142 (2010), 568–579.
5. Bessman, N.J., Bagchi, A., Ferguson, K.M., Lemmon, M.A., Complex relationship between ligand binding and dimerization in the epidermal growth factor receptor. Cell Rep. 9 (2014), 1306–1317.
6. Chen, L., Novicky, L., Merzlyakov, M., Hristov, T., Hristova, K., Measuring the energetics of membrane protein dimerization in mammalian membranes. J. Am. Chem. Soc. 132 (2010), 3628–3635.
7. Chen, L., Placone, J., Novicky, L., Hristova, K., The extracellular domain of fibroblast growth factor receptor 3 inhibits ligand-independent dimerization. Sci. Signal., 3, 2010, ra86.
8. Chung, I., Akita, R., Vandlen, R., Toomre, D., Schlessinger, J., Mellman, I., Spatial control of EGF receptor activation by reversible dimerization on living cells. Nature 464 (2010), 783–787.
9. Collaborative Computational Project, Number 4. The CCP4 suite: Programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50 (1994), 760–763.
10. Dawson, J.P., Berger, M.B., Lin, C.C., Schlessinger, J., Lemmon, M.A., Ferguson, K.M., Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface. Mol. Cell. Biol. 25 (2005), 7734–7742.
11. Del Piccolo, N., Placone, J., He, L., Agudelo, S.C., Hristova, K., Production of plasma membrane vesicles with chloride salts and their utility as a cell membrane mimetic for biophysical characterization of membrane protein interactions. Anal. Chem. 84 (2012), 8650–8655.
12. Doerner, A., Scheck, R., Schepartz, A., Growth factor identity is encoded by discrete coiled-coil rotamers in the EGFR juxtamembrane region. Chem. Biol. 22 (2015), 776–784.
13. Eden, E.R., White, I.J., Tsapara, A., Futter, C.E., Membrane contacts between endosomes and ER provide sites for PTP1B-epidermal growth factor receptor interaction. Nat. Cell Biol. 12 (2010), 267–272.
14. Elenius, K., Paul, S., Allison, G., Sun, J., Klagsbrun, M., Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 16 (1997), 1268–1278.
15. Emsley, P., Cowtan, K., Coot: Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60 (2004), 2126–2132.
16. Ferguson, K.M., Structure-based view of epidermal growth factor receptor regulation. Annu. Rev. Biophys. 37 (2008), 353–373.
17. Ferguson, K.M., Darling, P.J., Mohan, M.J., Macatee, T.L., Lemmon, M.A., Extracellular domains drive homo- but not hetero-dimerization of erbB receptors. EMBO J. 19 (2000), 4632–4643.
18. Ferguson, K.M., Berger, M.B., Mendrola, J.M., Cho, H.S., Leahy, D.J., Lemmon, M.A., EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol. Cell 11 (2003), 507–517.
19. Francavilla, C., Papetti, M., Rigbolt, K.T., Pedersen, A.K., Sigurdsson, J.O., Cazzamali, G., Karemore, G., Blagoev, B., Olsen, J.V., Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. Nat. Struct. Mol. Biol. 23 (2016), 608–618.
20. Furness, S.G.B., Liang, Y.L., Nowell, C.J., Halls, M.L., Wookey, P.J., Dal Maso, E., Inoue, A., Christopoulos, A., Wootten, D., Sexton, P.M., Ligand-dependent modulation of G protein conformation alters drug efficacy. Cell 167 (2016), 739–749.e11.
21. Garrett, T.P.J., McKern, N.M., Lou, M., Elleman, T.C., Adams, T.E., Lovrecz, G.O., Zhu, H.J., Walker, F., Frenkel, M.J., Hoyne, P.A., et al. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell 110 (2002), 763–773.
22. Garrett, T.P.J., McKern, N.M., Lou, M., Elleman, T.C., Adams, T.E., Lovrecz, G.O., Kofler, M., Jorissen, R.N., Nice, E.C., Burgess, A.W., Ward, C.W., The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell 11 (2003), 495–505.
23. Harris, R.C., Chung, E., Coffey, R.J., EGF receptor ligands. Exp. Cell Res. 284 (2003), 2–13.
24. Herrero, A., Casar, B., Colón-Bolea, P., Agudo-Ibáñez, L., Crespo, P., Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells. Mol. Biol. Cell 27 (2016), 1958–1968.
25. Ho, C.C.M., Chhabra, A., Starkl, P., Schnorr, P.J., Wilmes, S., Moraga, I., Kwon, H.S., Gaudenzio, N., Sibilano, R., Wehrman, T.S., et al. Decoupling the functional pleiotropy of stem cell factor by tuning c-Kit signaling. Cell 168 (2017), 1041–1052.e18.
26. Kavran, J.M., McCabe, J.M., Byrne, P.O., Connacher, M.K., Wang, Z., Ramek, A., Sarabipour, S., Shan, Y., Shaw, D.E., Hristova, K., et al. How IGF-1 activates its receptor. eLife, 3, 2014, e03772.
27. Kholodenko, B.N., Demin, O.V., Moehren, G., Hoek, J.B., Quantification of short term signaling by the epidermal growth factor receptor. J. Biol. Chem. 274 (1999), 30169–30181.
28. Kim, A.R., Ulirsch, J.C., Wilmes, S., Unal, E., Moraga, I., Karakukcu, M., Yuan, D., Kazerounian, S., Abdulhay, N.J., King, D.S., et al. Functional selectivity in cytokine signaling revealed through a pathogenic EPO mutation. Cell 168 (2017), 1053–1064.e15.
29. Klein, D.E., Stayrook, S.E., Shi, F., Narayan, K., Lemmon, M.A., Structural basis for EGFR ligand sequestration by Argos. Nature 453 (2008), 1271–1275.
30. Klein Herenbrink, C., Sykes, D.A., Donthamsetti, P., Canals, M., Coudrat, T., Shonberg, J., Scammells, P.J., Capuano, B., Sexton, P.M., Charlton, S.J., et al. The role of kinetic context in apparent biased agonism at GPCRs. Nat. Commun., 7, 2016, 10842.
31. Knudsen, S.L., Mac, A.S., Henriksen, L., van Deurs, B., Grøvdal, L.M., EGFR signaling patterns are regulated by its different ligands. Growth Factors 32 (2014), 155–163.
32. Kochupurakkal, B.S., Harari, D., Di-Segni, A., Maik-Rachline, G., Lyass, L., Gur, G., Kerber, G., Citri, A., Lavi, S., Eilam, R., et al. Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity. J. Biol. Chem. 280 (2005), 8503–8512.
33. Komurasaki, T., Toyoda, H., Uchida, D., Morimoto, S., Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene 15 (1997), 2841–2848.
34. Konarev, P.V., Volkov, V.V., Sokolova, A.V., Koch, M.H.J., Svergun, D.I., PRIMUS: A Windows PC-based system for small-angle scattering data analysis. J. Appl. Cryst. 36 (2003), 1277–1282.
35. Kovacs, E., Zorn, J.A., Huang, Y., Barros, T., Kuriyan, J., A structural perspective on the regulation of the epidermal growth factor receptor. Annu. Rev. Biochem. 84 (2015), 739–764.
36. Lane, J.R., May, L.T., Parton, R.G., Sexton, P.M., Christopoulos, A., A kinetic view of GPCR allostery and biased agonism. Nat. Chem. Biol. 13 (2017), 929–937.
37. Lemmon, M.A., Schlessinger, J., Cell signaling by receptor tyrosine kinases. Cell 141 (2010), 1117–1134.
38. Lemmon, M.A., Bu, Z., Ladbury, J.E., Zhou, M., Pinchasi, D., Lax, I., Engelman, D.M., Schlessinger, J., Two EGF molecules contribute additively to stabilization of the EGFR dimer. EMBO J. 16 (1997), 281–294.
39. Lemmon, M.A., Freed, D.M., Schlessinger, J., Kiyatkin, A., The dark side of cell signaling: Positive roles for negative regulators. Cell 164 (2016), 1172–1184.
40. Liu, P., Cleveland, T.E. 4th, Bouyain, S., Byrne, P.O., Longo, P.A., Leahy, D.J., A single ligand is sufficient to activate EGFR dimers. Proc. Natl. Acad. Sci. USA 109 (2012), 10861–10866.
41. Low-Nam, S.T., Lidke, K.A., Cutler, P.J., Roovers, R.C., van Bergen en Henegouwen, P.M., Wilson, B.S., Lidke, D.S., ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding. Nat. Struct. Mol. Biol. 18 (2011), 1244–1249.
42. Lu, C., Mi, L.Z., Grey, M.J., Zhu, J., Graef, E., Yokoyama, S., Springer, T.A., Structural evidence for loose linkage between ligand binding and kinase activation in the epidermal growth factor receptor. Mol. Cell. Biol. 30 (2010), 5432–5443.
43. Lu, C., Mi, L.Z., Schürpf, T., Walz, T., Springer, T.A., Mechanisms for kinase-mediated dimerization of the epidermal growth factor receptor. J. Biol. Chem. 287 (2012), 38244–38253.
44. Macdonald-Obermann, J.L., Pike, L.J., Different epidermal growth factor (EGF) receptor ligands show distinct kinetics and biased or partial agonism for homodimer and heterodimer formation. J. Biol. Chem. 289 (2014), 26178–26188.
45. Manglik, A., Kim, T.H., Masureel, M., Altenbach, C., Yang, Z., Hilger, D., Lerch, M.T., Kobilka, T.S., Thian, F.S., Hubbell, W.L., et al. Structural insights into the dynamic process of β2-adrenergic receptor signaling. Cell 161 (2015), 1101–1111.
46. Marshall, C.J., Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell 80 (1995), 179–185.
47. McKeithan, T.W., Kinetic proofreading in T-cell receptor signal transduction. Proc. Natl. Acad. Sci. USA 92 (1995), 5042–5046.
48. Mi, L.Z., Lu, C., Li, Z., Nishida, N., Walz, T., Springer, T.A., Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor. Nat. Struct. Mol. Biol. 18 (2011), 984–989.
49. Nagashima, T., Shimodaira, H., Ide, K., Nakakuki, T., Tani, Y., Takahashi, K., Yumoto, N., Hatakeyama, M., Quantitative transcriptional control of ErbB receptor signaling undergoes graded to biphasic response for cell differentiation. J. Biol. Chem. 282 (2007), 4045–4056.
50. Nygaard, R., Zou, Y., Dror, R.O., Mildorf, T.J., Arlow, D.H., Manglik, A., Pan, A.C., Liu, C.W., Fung, J.J., Bokoch, M.P., et al. The dynamic process of β(2)-adrenergic receptor activation. Cell 152 (2013), 532–542.
51. Ogiso, H., Ishitani, R., Nureki, O., Fukai, S., Yamanaka, M., Kim, J.H., Saito, K., Sakamoto, A., Inoue, M., Shirouzu, M., Yokoyama, S., Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 110 (2002), 775–787.
52. Red Brewer, M., Choi, S.H., Alvarado, D., Moravcevic, K., Pozzi, A., Lemmon, M.A., Carpenter, G., The juxtamembrane region of the EGF receptor functions as an activation domain. Mol. Cell 34 (2009), 641–651.
53. Riese, D.J. 2nd, Cullum, R.L., Epiregulin: Roles in normal physiology and cancer. Semin. Cell Dev. Biol. 28 (2014), 49–56.
54. Riese, D.J. 2nd, Bermingham, Y., van Raaij, T.M., Buckley, S., Plowman, G.D., Stern, D.F., Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. Oncogene 12 (1996), 345–353.
55. Rizzi, M., Pittarella, P., Sabbatini, M., Renò, F., Epiregulin induces human SK-N-BE cell differentiation through ERK1/2 signaling pathway. Growth Factors 31 (2013), 90–97.
56. Roepstorff, K., Grandal, M.V., Henriksen, L., Knudsen, S.L., Lerdrup, M., Grøvdal, L., Willumsen, B.M., van Deurs, B., Differential effects of EGFR ligands on endocytic sorting of the receptor. Traffic 10 (2009), 1115–1127.
57. Ronan, T., Macdonald-Obermann, J.L., Huelsmann, L., Bessman, N.J., Naegle, K.M., Pike, L.J., Different epidermal growth factor receptor (EGFR) agonists produce unique signatures for the recruitment of downstream signaling proteins. J. Biol. Chem. 291 (2016), 5528–5540.
58. Scheck, R.A., Lowder, M.A., Appelbaum, J.S., Schepartz, A., Bipartite tetracysteine display reveals allosteric control of ligand-specific EGFR activation. ACS Chem. Biol. 7 (2012), 1367–1376.
59. Shi, T., Niepel, M., McDermott, J.E., Gao, Y., Nicora, C.D., Chrisler, W.B., Markillie, L.M., Petyuk, V.A., Smith, R.D., Rodland, K.D., et al. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway. Sci. Signal., 9, 2016, rs6.
60. Sparta, B., Pargett, M., Minguet, M., Distor, K., Bell, G., Albeck, J.G., Receptor level mechanisms are required for epidermal growth factor (EGF)-stimulated extracellular signal-regulated kinase (ERK) activity pulses. J. Biol. Chem. 290 (2015), 24784–24792.
61. Swain, P.S., Siggia, E.D., The role of proofreading in signal transduction specificity. Biophys. J. 82 (2002), 2928–2933.
62. Sweeney, C., Carraway, K.L. 3rd, Ligand discrimination by ErbB receptors: Differential signaling through differential phosphorylation site usage. Oncogene 19 (2000), 5568–5573.
63. Valley, C.C., Arndt-Jovin, D.J., Karedla, N., Steinkamp, M.P., Chizhik, A.I., Hlavacek, W.S., Wilson, B.S., Lidke, K.A., Lidke, D.S., Enhanced dimerization drives ligand-independent activity of mutant epidermal growth factor receptor in lung cancer. Mol. Biol. Cell 26 (2015), 4087–4099.
64. Wacker, D., Stevens, R.C., Roth, B.L., How ligands illuminate GPCR molecular pharmacology. Cell 170 (2017), 414–427.
65. Willmarth, N.E., Ethier, S.P., Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells. J. Biol. Chem. 281 (2006), 37728–37737.
66. Wilson, K.J., Gilmore, J.L., Foley, J., Lemmon, M.A., Riese, D.J. 2nd, Functional selectivity of EGF family peptide growth factors: Implications for cancer. Pharmacol. Ther. 122 (2009), 1–8.
67. Wilson, K.J., Mill, C., Lambert, S., Buchman, J., Wilson, T.R., Hernandez-Gordillo, V., Gallo, R.M., Ades, L.M., Settleman, J., Riese, D.J. 2nd, EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling. Growth Factors 30 (2012), 107–116.
68. Wolber, P.K., Hudson, B.S., An analytic solution to the Förster energy transfer problem in two dimensions. Biophys. J. 28 (1979), 197–210.