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. 2000 Feb;9(2):310–324. doi: 10.1110/ps.9.2.310

Characterization of a comparative model of the extracellular domain of the epidermal growth factor receptor.

R N Jorissen 1, V C Epa 1, H R Treutlein 1, T P Garrett 1, C W Ward 1, A W Burgess 1
PMCID: PMC2144539  PMID: 10716183

Abstract

The Epidermal Growth Factor (EGF) receptor is a tyrosine kinase that mediates the biological effects of ligands such as EGF and transforming growth factor alpha. An understanding of the molecular basis of its action has been hindered by a lack of structural and mutational data on the receptor. We have constructed comparative models of the four extracellular domains of the EGF receptor that are based on the structure of the first three domains of the insulin-like growth factor-1 (IGF-1) receptor. The first and third domains of the EGF receptor, L1 and L2, are right-handed beta helices. The second and fourth domains of the EGF receptor, S1 and S2, consist of the modules held together by disulfide bonds, which, except for the first module of the S1 domain, form rod-like structures. The arrangement of the L1 and S1 domains of the model are similar to that of the first two domains of the IGF-1 receptor, whereas that of the L2 and S2 domains appear to be significantly different. Using the EGF receptor model and limited information from the literature, we have proposed a number of regions that may be involved in the functioning of the receptor. In particular, the faces containing the large beta sheets in the L1 and L2 domains have been suggested to be involved with ligand binding of EGF to its receptor.

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Selected References

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  1. Abe Y., Odaka M., Inagaki F., Lax I., Schlessinger J., Kohda D. Disulfide bond structure of human epidermal growth factor receptor. J Biol Chem. 1998 May 1;273(18):11150–11157. doi: 10.1074/jbc.273.18.11150. [DOI] [PubMed] [Google Scholar]
  2. Alroy I., Yarden Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997 Jun 23;410(1):83–86. doi: 10.1016/s0014-5793(97)00412-2. [DOI] [PubMed] [Google Scholar]
  3. Anzano M. A., Roberts A. B., Smith J. M., Sporn M. B., De Larco J. E. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6264–6268. doi: 10.1073/pnas.80.20.6264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bajaj M., Waterfield M. D., Schlessinger J., Taylor W. R., Blundell T. On the tertiary structure of the extracellular domains of the epidermal growth factor and insulin receptors. Biochim Biophys Acta. 1987 Nov 26;916(2):220–226. doi: 10.1016/0167-4838(87)90112-9. [DOI] [PubMed] [Google Scholar]
  5. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  6. Bowie J. U., Lüthy R., Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science. 1991 Jul 12;253(5016):164–170. doi: 10.1126/science.1853201. [DOI] [PubMed] [Google Scholar]
  7. Burden S., Yarden Y. Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis. Neuron. 1997 Jun;18(6):847–855. doi: 10.1016/s0896-6273(00)80324-4. [DOI] [PubMed] [Google Scholar]
  8. Carpenter G., Cohen S. Epidermal growth factor. J Biol Chem. 1990 May 15;265(14):7709–7712. [PubMed] [Google Scholar]
  9. Degenhardt M., Weber W., Eschenburg S., Dierks K., Funari S. S., Rapp G., Betzel C. Crystallization and preliminary X-ray crystallographic analysis of the EGF receptor ectodomain. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):999–1001. doi: 10.1107/s0907444998001851. [DOI] [PubMed] [Google Scholar]
  10. Derynck R., Roberts A. B., Winkler M. E., Chen E. Y., Goeddel D. V. Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287–297. doi: 10.1016/0092-8674(84)90550-6. [DOI] [PubMed] [Google Scholar]
  11. Eisbacher M., Khachigian L. M., Khin T. H., Holmes M. L., Chong B. H. Inducible expression of the megakaryocyte-specific gene glycoprotein IX is mediated through an Ets binding site and involves upstream activation of extracellular signal-regulated kinase. Cell Growth Differ. 2001 Aug;12(8):435–445. [PubMed] [Google Scholar]
  12. Etzold T., Argos P. SRS--an indexing and retrieval tool for flat file data libraries. Comput Appl Biosci. 1993 Feb;9(1):49–57. doi: 10.1093/bioinformatics/9.1.49. [DOI] [PubMed] [Google Scholar]
  13. Fernandez R., Tabarini D., Azpiazu N., Frasch M., Schlessinger J. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J. 1995 Jul 17;14(14):3373–3384. doi: 10.1002/j.1460-2075.1995.tb07343.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garrett T. P., McKern N. M., Lou M., Frenkel M. J., Bentley J. D., Lovrecz G. O., Elleman T. C., Cosgrove L. J., Ward C. W. Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor. Nature. 1998 Jul 23;394(6691):395–399. doi: 10.1038/28668. [DOI] [PubMed] [Google Scholar]
  15. Grandis J. R., Tweardy D. J. TGF-alpha and EGFR in head and neck cancer. J Cell Biochem Suppl. 1993;17F:188–191. doi: 10.1002/jcb.240531027. [DOI] [PubMed] [Google Scholar]
  16. Greenfield C., Hiles I., Waterfield M. D., Federwisch M., Wollmer A., Blundell T. L., McDonald N. Epidermal growth factor binding induces a conformational change in the external domain of its receptor. EMBO J. 1989 Dec 20;8(13):4115–4123. doi: 10.1002/j.1460-2075.1989.tb08596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Groenen L. C., Nice E. C., Burgess A. W. Structure-function relationships for the EGF/TGF-alpha family of mitogens. Growth Factors. 1994;11(4):235–257. doi: 10.3109/08977199409010997. [DOI] [PubMed] [Google Scholar]
  18. Gullick W. J., Marsden J. J., Whittle N., Ward B., Bobrow L., Waterfield M. D. Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res. 1986 Jan;46(1):285–292. [PubMed] [Google Scholar]
  19. Günther N., Betzel C., Weber W. The secreted form of the epidermal growth factor receptor. Characterization and crystallization of the receptor-ligand complex. J Biol Chem. 1990 Dec 25;265(36):22082–22085. [PubMed] [Google Scholar]
  20. Haeder M., Rotsch M., Bepler G., Hennig C., Havemann K., Heimann B., Moelling K. Epidermal growth factor receptor expression in human lung cancer cell lines. Cancer Res. 1988 Mar 1;48(5):1132–1136. [PubMed] [Google Scholar]
  21. Harte M. T., Gentry L. E. Mutations within subdomain II of the extracellular region of epidermal growth factor receptor selectively alter TGF alpha binding. Arch Biochem Biophys. 1995 Oct 1;322(2):378–389. doi: 10.1006/abbi.1995.1478. [DOI] [PubMed] [Google Scholar]
  22. Hendlich M., Lackner P., Weitckus S., Floeckner H., Froschauer R., Gottsbacher K., Casari G., Sippl M. J. Identification of native protein folds amongst a large number of incorrect models. The calculation of low energy conformations from potentials of mean force. J Mol Biol. 1990 Nov 5;216(1):167–180. doi: 10.1016/S0022-2836(05)80068-3. [DOI] [PubMed] [Google Scholar]
  23. Huang H. S., Nagane M., Klingbeil C. K., Lin H., Nishikawa R., Ji X. D., Huang C. M., Gill G. N., Wiley H. S., Cavenee W. K. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol Chem. 1997 Jan 31;272(5):2927–2935. doi: 10.1074/jbc.272.5.2927. [DOI] [PubMed] [Google Scholar]
  24. Humphrey P. A., Gangarosa L. M., Wong A. J., Archer G. E., Lund-Johansen M., Bjerkvig R., Laerum O. D., Friedman H. S., Bigner D. D. Deletion-mutant epidermal growth factor receptor in human gliomas: effects of type II mutation on receptor function. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1413–1420. doi: 10.1016/0006-291x(91)91051-d. [DOI] [PubMed] [Google Scholar]
  25. King A. C., Cuatrecasas P. Resolution of high and low affinity epidermal growth factor receptors. Inhibition of high affinity component by low temperature, cycloheximide, and phorbol esters. J Biol Chem. 1982 Mar 25;257(6):3053–3060. [PubMed] [Google Scholar]
  26. King C. R., Kraus M. H., Williams L. T., Merlino G. T., Pastan I. H., Aaronson S. A. Human tumor cell lines with EGF receptor gene amplification in the absence of aberrant sized mRNAs. Nucleic Acids Res. 1985 Dec 9;13(23):8477–8486. doi: 10.1093/nar/13.23.8477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kline T. P., Brown F. K., Brown S. C., Jeffs P. W., Kopple K. D., Mueller L. Solution structures of human transforming growth factor alpha derived from 1H NMR data. Biochemistry. 1990 Aug 28;29(34):7805–7813. doi: 10.1021/bi00486a005. [DOI] [PubMed] [Google Scholar]
  28. Kohda D., Inagaki F. Three-dimensional nuclear magnetic resonance structures of mouse epidermal growth factor in acidic and physiological pH solutions. Biochemistry. 1992 Dec 1;31(47):11928–11939. doi: 10.1021/bi00162a036. [DOI] [PubMed] [Google Scholar]
  29. Kohda D., Odaka M., Lax I., Kawasaki H., Suzuki K., Ullrich A., Schlessinger J., Inagaki F. A 40-kDa epidermal growth factor/transforming growth factor alpha-binding domain produced by limited proteolysis of the extracellular domain of the epidermal growth factor receptor. J Biol Chem. 1993 Jan 25;268(3):1976–1981. [PubMed] [Google Scholar]
  30. Korc M., Chandrasekar B., Yamanaka Y., Friess H., Buchier M., Beger H. G. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest. 1992 Oct;90(4):1352–1360. doi: 10.1172/JCI116001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kraus M. H., Issing W., Miki T., Popescu N. C., Aaronson S. A. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9193–9197. doi: 10.1073/pnas.86.23.9193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lax I., Bellot F., Honegger A. M., Schmidt A., Ullrich A., Givol D., Schlessinger J. Domain deletion in the extracellular portion of the EGF-receptor reduces ligand binding and impairs cell surface expression. Cell Regul. 1990 Jan;1(2):173–188. doi: 10.1091/mbc.1.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lax I., Bellot F., Howk R., Ullrich A., Givol D., Schlessinger J. Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. EMBO J. 1989 Feb;8(2):421–427. doi: 10.1002/j.1460-2075.1989.tb03393.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lax I., Fischer R., Ng C., Segre J., Ullrich A., Givol D., Schlessinger J. Noncontiguous regions in the extracellular domain of EGF receptor define ligand-binding specificity. Cell Regul. 1991 May;2(5):337–345. doi: 10.1091/mbc.2.5.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lax I., Mitra A. K., Ravera C., Hurwitz D. R., Rubinstein M., Ullrich A., Stroud R. M., Schlessinger J. Epidermal growth factor (EGF) induces oligomerization of soluble, extracellular, ligand-binding domain of EGF receptor. A low resolution projection structure of the ligand-binding domain. J Biol Chem. 1991 Jul 25;266(21):13828–13833. [PubMed] [Google Scholar]
  36. Layton J. E., Shimamoto G., Osslund T., Hammacher A., Smith D. K., Treutlein H. R., Boone T. Interaction of granulocyte colony-stimulating factor (G-CSF) with its receptor. Evidence that Glu19 of G-CSF interacts with Arg288 of the receptor. J Biol Chem. 1999 Jun 18;274(25):17445–17451. doi: 10.1074/jbc.274.25.17445. [DOI] [PubMed] [Google Scholar]
  37. 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. 1997 Jan 15;16(2):281–294. doi: 10.1093/emboj/16.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lüthy R., Bowie J. U., Eisenberg D. Assessment of protein models with three-dimensional profiles. Nature. 1992 Mar 5;356(6364):83–85. doi: 10.1038/356083a0. [DOI] [PubMed] [Google Scholar]
  39. Malden L. T., Novak U., Kaye A. H., Burgess A. W. Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res. 1988 May 15;48(10):2711–2714. [PubMed] [Google Scholar]
  40. Merlino G. T., Xu Y. H., Ishii S., Clark A. J., Semba K., Toyoshima K., Yamamoto T., Pastan I. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 1984 Apr 27;224(4647):417–419. doi: 10.1126/science.6200934. [DOI] [PubMed] [Google Scholar]
  41. Messa C., Russo F., Caruso M. G., Di Leo A. EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma. Acta Oncol. 1998;37(3):285–289. doi: 10.1080/028418698429595. [DOI] [PubMed] [Google Scholar]
  42. Morgan D. O., Jarnagin K., Roth R. A. Purification and characterization of the receptor for insulin-like growth factor I. Biochemistry. 1986 Sep 23;25(19):5560–5564. doi: 10.1021/bi00367a032. [DOI] [PubMed] [Google Scholar]
  43. Moriai T., Kobrin M. S., Hope C., Speck L., Korc M. A variant epidermal growth factor receptor exhibits altered type alpha transforming growth factor binding and transmembrane signaling. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10217–10221. doi: 10.1073/pnas.91.21.10217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Moscatello D. K., Holgado-Madruga M., Godwin A. K., Ramirez G., Gunn G., Zoltick P. W., Biegel J. A., Hayes R. L., Wong A. J. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 1995 Dec 1;55(23):5536–5539. [PubMed] [Google Scholar]
  45. Naismith J. H., Devine T. Q., Brandhuber B. J., Sprang S. R. Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor. J Biol Chem. 1995 Jun 2;270(22):13303–13307. doi: 10.1074/jbc.270.22.13303. [DOI] [PubMed] [Google Scholar]
  46. Odaka M., Kohda D., Lax I., Schlessinger J., Inagaki F. Ligand-binding enhances the affinity of dimerization of the extracellular domain of the epidermal growth factor receptor. J Biochem. 1997 Jul;122(1):116–121. doi: 10.1093/oxfordjournals.jbchem.a021718. [DOI] [PubMed] [Google Scholar]
  47. Peles E., Yarden Y. Neu and its ligands: from an oncogene to neural factors. Bioessays. 1993 Dec;15(12):815–824. doi: 10.1002/bies.950151207. [DOI] [PubMed] [Google Scholar]
  48. Plowman G. D., Culouscou J. M., Whitney G. S., Green J. M., Carlton G. W., Foy L., Neubauer M. G., Shoyab M. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1746–1750. doi: 10.1073/pnas.90.5.1746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Riese D. J., 2nd, Stern D. F. Specificity within the EGF family/ErbB receptor family signaling network. Bioessays. 1998 Jan;20(1):41–48. doi: 10.1002/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  50. Roach P., Zick Y., Formisano P., Accili D., Taylor S. I., Gorden P. A novel human insulin receptor gene mutation uniquely inhibits insulin binding without impairing posttranslational processing. Diabetes. 1994 Sep;43(9):1096–1102. doi: 10.2337/diab.43.9.1096. [DOI] [PubMed] [Google Scholar]
  51. Sali A., Blundell T. L. Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol. 1993 Dec 5;234(3):779–815. doi: 10.1006/jmbi.1993.1626. [DOI] [PubMed] [Google Scholar]
  52. Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
  53. Schejter E. D., Segal D., Glazer L., Shilo B. Z. Alternative 5' exons and tissue-specific expression of the Drosophila EGF receptor homolog transcripts. Cell. 1986 Sep 26;46(7):1091–1101. doi: 10.1016/0092-8674(86)90709-9. [DOI] [PubMed] [Google Scholar]
  54. Schuler G. D., Altschul S. F., Lipman D. J. A workbench for multiple alignment construction and analysis. Proteins. 1991;9(3):180–190. doi: 10.1002/prot.340090304. [DOI] [PubMed] [Google Scholar]
  55. Sippl M. J. Recognition of errors in three-dimensional structures of proteins. Proteins. 1993 Dec;17(4):355–362. doi: 10.1002/prot.340170404. [DOI] [PubMed] [Google Scholar]
  56. Smith J. J., Derynck R., Korc M. Production of transforming growth factor alpha in human pancreatic cancer cells: evidence for a superagonist autocrine cycle. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7567–7570. doi: 10.1073/pnas.84.21.7567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Stetefeld J., Mayer U., Timpl R., Huber R. Crystal structure of three consecutive laminin-type epidermal growth factor-like (LE) modules of laminin gamma1 chain harboring the nidogen binding site. J Mol Biol. 1996 Apr 5;257(3):644–657. doi: 10.1006/jmbi.1996.0191. [DOI] [PubMed] [Google Scholar]
  58. Sugawa N., Ekstrand A. J., James C. D., Collins V. P. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602–8606. doi: 10.1073/pnas.87.21.8602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Summerfield A. E., Hudnall A. K., Lukas T. J., Guyer C. A., Staros J. V. Identification of residues of the epidermal growth factor receptor proximal to residue 45 of bound epidermal growth factor. J Biol Chem. 1996 Aug 16;271(33):19656–19659. doi: 10.1074/jbc.271.33.19656. [DOI] [PubMed] [Google Scholar]
  60. Tramontano A. Homology modeling with low sequence identity. Methods. 1998 Mar;14(3):293–300. doi: 10.1006/meth.1998.0585. [DOI] [PubMed] [Google Scholar]
  61. Tsai C. J., Lin S. L., Wolfson H. J., Nussinov R. Studies of protein-protein interfaces: a statistical analysis of the hydrophobic effect. Protein Sci. 1997 Jan;6(1):53–64. doi: 10.1002/pro.5560060106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tzahar E., Pinkas-Kramarski R., Moyer J. D., Klapper L. N., Alroy I., Levkowitz G., Shelly M., Henis S., Eisenstein M., Ratzkin B. J. Bivalence of EGF-like ligands drives the ErbB signaling network. EMBO J. 1997 Aug 15;16(16):4938–4950. doi: 10.1093/emboj/16.16.4938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Ullrich A., Bell J. R., Chen E. Y., Herrera R., Petruzzelli L. M., Dull T. J., Gray A., Coussens L., Liao Y. C., Tsubokawa M. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. 1985 Feb 28-Mar 6Nature. 313(6005):756–761. doi: 10.1038/313756a0. [DOI] [PubMed] [Google Scholar]
  64. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  65. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  66. Ward C. W., Hoyne P. A., Flegg R. H. Insulin and epidermal growth factor receptors contain the cysteine repeat motif found in the tumor necrosis factor receptor. Proteins. 1995 Jun;22(2):141–153. doi: 10.1002/prot.340220207. [DOI] [PubMed] [Google Scholar]
  67. Woltjer R. L., Lukas T. J., Staros J. V. Direct identification of residues of the epidermal growth factor receptor in close proximity to the amino terminus of bound epidermal growth factor. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7801–7805. doi: 10.1073/pnas.89.16.7801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wu D. G., Wang L. H., Chi Y., Sato G. H., Sato J. D. Human epidermal growth factor receptor residue covalently cross-linked to epidermal growth factor. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3151–3155. doi: 10.1073/pnas.87.8.3151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wu D. G., Wang L. H., Sato G. H., West K. A., Harris W. R., Crabb J. W., Sato J. D. Human epidermal growth factor (EGF) receptor sequence recognized by EGF competitive monoclonal antibodies. Evidence for the localization of the EGF-binding site. J Biol Chem. 1989 Oct 15;264(29):17469–17475. [PubMed] [Google Scholar]
  70. Yarden Y., Schlessinger J. Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation. Biochemistry. 1987 Mar 10;26(5):1434–1442. doi: 10.1021/bi00379a034. [DOI] [PubMed] [Google Scholar]
  71. Yoder M. D., Keen N. T., Jurnak F. New domain motif: the structure of pectate lyase C, a secreted plant virulence factor. Science. 1993 Jun 4;260(5113):1503–1507. doi: 10.1126/science.8502994. [DOI] [PubMed] [Google Scholar]

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