PDBsum entry 1mox

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protein ligands metals Protein-protein interface(s) links
Transferase/growth factor PDB id
Protein chains
499 a.a. *
49 a.a. *
_CL ×4
_CD ×11
_PT ×7
Waters ×79
* Residue conservation analysis
PDB id:
Name: Transferase/growth factor
Title: Crystal structure of human epidermal growth factor receptor 1-501) in complex with tgf-alpha
Structure: Epidermal growth factor receptor. Chain: a, b. Fragment: extracellular fragment. Engineered: yes. Transforming growth factor alpha. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: egfr. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: lec8. Gene: tgfa. Expressed in: escherichia coli.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.237     R-free:   0.289
Authors: T.P.J.Garrett,N.M.Mckern,M.Lou,T.C.Elleman,T.E.Adams,G.O.Lov J.Zhu,F.Walker,M.J.Frenkel,P.A.Hoyne,R.N.Jorissen,E.C.Nice, A.W.Burgess,C.W.Ward
Key ref:
T.P.Garrett et al. (2002). Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Cell, 110, 763-773. PubMed id: 12297049 DOI: 10.1016/S0092-8674(02)00940-6
10-Sep-02     Release date:   10-Sep-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor
1210 a.a.
499 a.a.
Protein chains
P01135  (TGFA_HUMAN) -  Protransforming growth factor alpha
160 a.a.
49 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Bound ligand (Het Group name = NAG)
matches with 47.62% similarity
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     ATP binding     2 terms  


DOI no: 10.1016/S0092-8674(02)00940-6 Cell 110:763-773 (2002)
PubMed id: 12297049  
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha.
T.P.Garrett, N.M.McKern, M.Lou, T.C.Elleman, T.E.Adams, G.O.Lovrecz, H.J.Zhu, F.Walker, M.J.Frenkel, P.A.Hoyne, R.N.Jorissen, E.C.Nice, A.W.Burgess, C.W.Ward.
We report the crystal structure, at 2.5 A resolution, of a truncated human EGFR ectodomain bound to TGFalpha. TGFalpha interacts with both L1 and L2 domains of EGFR, making many main chain contacts with L1 and interacting with L2 via key conserved residues. The results indicate how EGFR family members can bind a family of highly variable ligands. In the 2:2 TGFalpha:sEGFR501 complex, each ligand interacts with only one receptor molecule. There are two types of dimers in the asymmetric unit: a head-to-head dimer involving contacts between the L1 and L2 domains and a back-to-back dimer dominated by interactions between the CR1 domains of each receptor. Based on sequence conservation, buried surface area, and mutagenesis experiments, the back-to-back dimer is favored to be biologically relevant.
  Selected figure(s)  
Figure 4.
Figure 4. Stereo View of Ligand Cα TracesLigands were superimposed using the Cα atoms of core residues (see text). The Cα traces have been rotated 55° about a horizontal axis relative to Figure 5 and are as follows: TGFα molecules C (red with yellow disulfide bonds) and D (blue) from this study; minimized average NMR structure of TGFα (orange) from PDB:2TGF (Harvey et al., 1991); diphtheria toxin bound heparin binding EGF (gray) from PDB:1XDT (Louie et al., 1997); and crystallized human EGF molecule A (purple) and molecule B (green) from PDB:1JL9 (Lu et al., 2001). While the two TGFα molecules from this study (C and D), EGF molecule A of 1JL9, and hbEGF superimpose well from residue 14, the top half of the B loop adopts different conformations in the NMR structure (2TGF) and 1JL9:B (top of each panel). In the uncomplexed form, the N terminus of TGFα is structurally heterogeneous (bottom left of each panel).
Figure 6.
Figure 6. Stereo View of the Contacts between the CR1 Loop of EGFR Molecule A with CR1 of EGFR Molecule B in the Back-to-Back Dimer InterfaceCR1 loop of EGFR molecule A is shown in orange, and CR1 of EGFR molecule B is in gray. Interchain hydrogen bonds are drawn in black along with the hydrogen bond from Asn247 of molecule A (not labeled), which appears to stabilize the loop tip conformation. The single letter code and residue number is used for amino acid residues. The dimer axis lies vertically at the left at H280.
  The above figures are reprinted by permission from Cell Press: Cell (2002, 110, 763-773) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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21287620 N.Chennamsetty, V.Voynov, V.Kayser, B.Helk, and B.L.Trout (2011).
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20723758 D.Alvarado, D.E.Klein, and M.A.Lemmon (2010).
Structural basis for negative cooperativity in growth factor binding to an EGF receptor.
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PDB codes: 3ltf 3ltg
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In vitro enzymatic characterization of near full length EGFR in activated and inhibited states.
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19274663 C.W.Ward, and M.C.Lawrence (2009).
Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor.
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19718021 D.Alvarado, D.E.Klein, and M.A.Lemmon (2009).
ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor.
  Nature, 461, 287-291.
PDB code: 3i2t
19390622 J.F.Flynn, C.Wong, and J.M.Wu (2009).
Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer.
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19336395 J.L.Macdonald-Obermann, and L.J.Pike (2009).
The intracellular juxtamembrane domain of the epidermal growth factor (EGF) receptor is responsible for the allosteric regulation of EGF binding.
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19196031 J.L.Macdonald-Obermann, and L.J.Pike (2009).
Palmitoylation of the EGF receptor impairs signal transduction and abolishes high-affinity ligand binding.
  Biochemistry, 48, 2505-2513.  
19135477 K.J.Wilson, J.L.Gilmore, J.Foley, M.A.Lemmon, and D.J.Riese (2009).
Functional selectivity of EGF family peptide growth factors: implications for cancer.
  Pharmacol Ther, 122, 1-8.  
18992239 K.R.Schmitz, and K.M.Ferguson (2009).
Interaction of antibodies with ErbB receptor extracellular regions.
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19171934 K.S.Yang, M.X.Ilagan, D.Piwnica-Worms, and L.J.Pike (2009).
Luciferase fragment complementation imaging of conformational changes in the epidermal growth factor receptor.
  J Biol Chem, 284, 7474-7482.  
19038249 M.A.Lemmon (2009).
Ligand-induced ErbB receptor dimerization.
  Exp Cell Res, 315, 638-648.  
19056486 M.Murillo-Carretero, A.Torroglosa, C.Castro, A.Villalobo, and C.Estrada (2009).
S-Nitrosylation of the epidermal growth factor receptor: a regulatory mechanism of receptor tyrosine kinase activity.
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20477507 M.Yamauchi, and N.Gotoh (2009).
Theme: oncology--molecular mechanisms determining the efficacy of EGF receptor-specific tyrosine kinase inhibitors help to identify biomarker candidates.
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  19048033 P.Jin, J.Zhang, M.Beryt, L.Turin, C.Brdlik, Y.Feng, X.Bai, J.Liu, B.Jorgensen, and H.M.Shepard (2009).
Rational optimization of a bispecific ligand trap targeting EGF receptor family ligands.
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18761339 R.Bose, and X.Zhang (2009).
The ErbB kinase domain: structural perspectives into kinase activation and inhibition.
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19289058 S.E.Telesco, and R.Radhakrishnan (2009).
Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.
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19115345 T.C.Lee, and D.W.Threadgill (2009).
Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor.
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19289842 T.P.Garrett, A.W.Burgess, H.K.Gan, R.B.Luwor, G.Cartwright, F.Walker, S.G.Orchard, A.H.Clayton, E.C.Nice, J.Rothacker, B.Catimel, W.K.Cavenee, L.J.Old, E.Stockert, G.Ritter, T.E.Adams, P.A.Hoyne, D.Wittrup, G.Chao, J.R.Cochran, C.Luo, M.Lou, T.Huyton, Y.Xu, W.D.Fairlie, S.Yao, A.M.Scott, and T.G.Johns (2009).
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PDB codes: 3g5v 3g5x 3g5y 3g5z
19258037 V.Ratushny, I.Astsaturov, B.A.Burtness, E.A.Golemis, and J.S.Silverman (2009).
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PDB codes: 3bbt 3bbw 3bce
18500331 D.E.Klein, S.E.Stayrook, F.Shi, K.Narayan, and M.A.Lemmon (2008).
Structural basis for EGFR ligand sequestration by Argos.
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PDB codes: 3c9a 3ca7 3cgu
18942860 E.Park, R.Baron, and R.Landgraf (2008).
Higher-order association states of cellular ERBB3 probed with photo-cross-linkable aptamers.
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18755034 H.Conzelmann, D.Fey, and E.D.Gilles (2008).
Exact model reduction of combinatorial reaction networks.
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18199660 I.Iloro, D.Narváez, N.Guillén, C.M.Camacho, L.Guillén, E.Cora, and B.Pastrana-Ríos (2008).
The kinetics of the hydrogen/deuterium exchange of epidermal growth factor receptor ligands.
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18427122 J.J.Lammerts van Bueren, W.K.Bleeker, A.Brännström, A.von Euler, M.Jansson, M.Peipp, T.Schneider-Merck, T.Valerius, J.G.van de Winkel, and P.W.Parren (2008).
The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility.
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18165319 J.L.Macdonald, and L.J.Pike (2008).
Heterogeneity in EGF-binding affinities arises from negative cooperativity in an aggregating system.
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18394559 J.Schmiedel, A.Blaukat, S.Li, T.Knöchel, and K.M.Ferguson (2008).
Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization.
  Cancer Cell, 13, 365-373.
PDB codes: 3c08 3c09
18773073 K.Buac, D.E.Watkins-Chow, S.K.Loftus, D.M.Larson, A.Incao, G.Gibney, and W.J.Pavan (2008).
A Sox10 expression screen identifies an amino acid essential for Erbb3 function.
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18573086 K.M.Ferguson (2008).
Structure-based view of epidermal growth factor receptor regulation.
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18288481 K.Roepstorff, L.Grøvdal, M.Grandal, M.Lerdrup, and B.van Deurs (2008).
Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer.
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18771282 L.Z.Mi, M.J.Grey, N.Nishida, T.Walz, C.Lu, and T.A.Springer (2008).
Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs.
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18347020 M.Gangloff, A.Murali, J.Xiong, C.J.Arnot, A.N.Weber, A.M.Sandercock, C.V.Robinson, R.Sarisky, A.Holzenburg, C.Kao, and N.J.Gay (2008).
Structural insight into the mechanism of activation of the Toll receptor by the dimeric ligand Spätzle.
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18259690 M.J.Wieduwilt, and M.M.Moasser (2008).
The epidermal growth factor receptor family: biology driving targeted therapeutics.
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18031935 M.Landau, and N.Ben-Tal (2008).
Dynamic equilibrium between multiple active and inactive conformations explains regulation and oncogenic mutations in ErbB receptors.
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17684490 N.V.Hayes, R.J.Newsam, A.J.Baines, and W.J.Gullick (2008).
Characterization of the cell membrane-associated products of the Neuregulin 4 gene.
  Oncogene, 27, 715-720.  
18365190 O.Samna Soumana, N.Garnier, and M.Genest (2008).
Insight into the recognition patterns of the ErbB receptor family transmembrane domains: heterodimerization models through molecular dynamics search.
  Eur Biophys J, 37, 851-864.  
18230610 P.Cironi, I.A.Swinburne, and P.A.Silver (2008).
Enhancement of cell type specificity by quantitative modulation of a chimeric ligand.
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18412625 R.E.van Kesteren, J.S.Gagatek, A.Hagendorf, Y.Gouwenberg, A.B.Smit, and N.I.Syed (2008).
Postsynaptic expression of an epidermal growth factor receptor regulates cholinergic synapse formation between identified molluscan neurons.
  Eur J Neurosci, 27, 2043-2056.  
17890389 S.E.Webb, S.K.Roberts, S.R.Needham, C.J.Tynan, D.J.Rolfe, M.D.Winn, D.T.Clarke, R.Barraclough, and M.L.Martin-Fernandez (2008).
Single-molecule imaging and fluorescence lifetime imaging microscopy show different structures for high- and low-affinity epidermal growth factor receptors in A431 cells.
  Biophys J, 94, 803-819.  
18275813 S.Li, P.Kussie, and K.M.Ferguson (2008).
Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8.
  Structure, 16, 216-227.
PDB codes: 3b2u 3b2v
18847225 T.Yamamoto, H.C.Chen, E.Guigard, C.M.Kay, and R.O.Ryan (2008).
Molecular studies of pH-dependent ligand interactions with the low-density lipoprotein receptor.
  Biochemistry, 47, 11647-11652.  
18762250 X.Li, Y.Huang, J.Jiang, and S.J.Frank (2008).
ERK-dependent threonine phosphorylation of EGF receptor modulates receptor downregulation and signaling.
  Cell Signal, 20, 2145-2155.  
18039657 Y.X.Fan, L.Wong, J.Ding, N.A.Spiridonov, R.C.Johnson, and G.R.Johnson (2008).
Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism.
  J Biol Chem, 283, 1588-1596.  
17311283 A.K.Iyer, K.T.Tran, C.W.Borysenko, M.Cascio, C.J.Camacho, H.C.Blair, I.Bahar, and A.Wells (2007).
Tenascin cytotactin epidermal growth factor-like repeat binds epidermal growth factor receptor with low affinity.
  J Cell Physiol, 211, 748-758.  
17096356 A.Kolb, J.Kleeff, N.Arnold, N.A.Giese, T.Giese, M.Korc, and H.Friess (2007).
Expression and differential signaling of heregulins in pancreatic cancer cells.
  Int J Cancer, 120, 514-523.  
17555368 B.Burtness (2007).
Her signaling in pancreatic cancer.
  Expert Opin Biol Ther, 7, 823-829.  
17280834 C.W.Ward, M.C.Lawrence, V.A.Streltsov, T.E.Adams, and N.M.McKern (2007).
The insulin and EGF receptor structures: new insights into ligand-induced receptor activation.
  Trends Biochem Sci, 32, 129-137.  
18059449 D.J.Leahy (2007).
A monkey wrench in the kinase machine.
  Nat Struct Mol Biol, 14, 1120-1121.  
17288526 D.S.Hirsch, and W.J.Wu (2007).
Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy.
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17314037 E.M.Bublil, and Y.Yarden (2007).
The EGF receptor family: spearheading a merger of signaling and therapeutics.
  Curr Opin Cell Biol, 19, 124-134.  
17092939 H.K.Gan, F.Walker, A.W.Burgess, A.Rigopoulos, A.M.Scott, and T.G.Johns (2007).
The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 increases the formation of inactive untethered EGFR dimers. Implications for combination therapy with monoclonal antibody 806.
  J Biol Chem, 282, 2840-2850.  
17671639 H.Zhang, A.Berezov, Q.Wang, G.Zhang, J.Drebin, R.Murali, and M.I.Greene (2007).
ErbB receptors: from oncogenes to targeted cancer therapies.
  J Clin Invest, 117, 2051-2058.  
18059446 I.Amit, R.Wides, and Y.Yarden (2007).
Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy.
  Mol Syst Biol, 3, 151.  
18075577 J.Kuriyan, and D.Eisenberg (2007).
The origin of protein interactions and allostery in colocalization.
  Nature, 450, 983-990.  
  19662225 J.M.Kneller, T.Ehlen, J.P.Matisic, D.Miller, D.Van Niekerk, W.L.Lam, M.Marra, R.Richards-Kortum, M.Follen, C.Macaulay, and S.J.Jones (2007).
Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling.
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17697999 J.P.Dawson, Z.Bu, and M.A.Lemmon (2007).
Ligand-induced structural transitions in ErbB receptor extracellular domains.
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17439940 L.Ivanisevic, W.Zheng, S.B.Woo, K.E.Neet, and H.U.Saragovi (2007).
TrkA receptor "hot spots" for binding of NT-3 as a heterologous ligand.
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17306385 M.Katz, I.Amit, and Y.Yarden (2007).
Regulation of MAPKs by growth factors and receptor tyrosine kinases.
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17468161 P.Liu, T.Sudhaharan, R.M.Koh, L.C.Hwang, S.Ahmed, I.N.Maruyama, and T.Wohland (2007).
Investigation of the dimerization of proteins from the epidermal growth factor receptor family by single wavelength fluorescence cross-correlation spectroscopy.
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17274834 R.Landgraf (2007).
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks.
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17339314 S.J.Chan, S.Nakagawa, and D.F.Steiner (2007).
Complementation analysis demonstrates that insulin cross-links both alpha subunits in a truncated insulin receptor dimer.
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17496034 S.Saffarian, Y.Li, E.L.Elson, and L.J.Pike (2007).
Oligomerization of the EGF receptor investigated by live cell fluorescence intensity distribution analysis.
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17804794 W.D.Tolbert, J.Daugherty, C.Gao, Q.Xie, C.Miranti, E.Gherardi, G.V.Woude, and H.E.Xu (2007).
A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist.
  Proc Natl Acad Sci U S A, 104, 14592-14597.
PDB codes: 2qj2 2qj4
17553674 W.Liu, K.Zscheppang, S.Murray, H.C.Nielsen, and C.E.Dammann (2007).
The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells.
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16829981 A.Citri, and Y.Yarden (2006).
EGF-ERBB signalling: towards the systems level.
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16531225 A.Sivasubramanian, G.Chao, H.M.Pressler, K.D.Wittrup, and J.J.Gray (2006).
Structural model of the mAb 806-EGFR complex using computational docking followed by computational and experimental mutagenesis.
  Structure, 14, 401-414.
PDB codes: 2exp 2exq
16825199 C.M.Warren, K.Kani, and R.Landgraf (2006).
The N-terminal domains of neuregulin 1 confer signal attenuation.
  J Biol Chem, 281, 27306-27316.  
16963452 C.Zahnd, F.Pecorari, N.Straumann, E.Wyler, and A.Plückthun (2006).
Selection and characterization of Her2 binding-designed ankyrin repeat proteins.
  J Biol Chem, 281, 35167-35175.  
16537482 E.Gherardi, S.Sandin, M.V.Petoukhov, J.Finch, M.E.Youles, L.G.Ofverstedt, R.N.Miguel, T.L.Blundell, G.F.Vande Woude, U.Skoglund, and D.I.Svergun (2006).
Structural basis of hepatocyte growth factor/scatter factor and MET signalling.
  Proc Natl Acad Sci U S A, 103, 4046-4051.
PDB codes: 2ced 2cee 2ceg 2cew
16533841 H.Shankaran, H.S.Wiley, and H.Resat (2006).
Modeling the effects of HER/ErbB1-3 coexpression on receptor dimerization and biological response.
  Biophys J, 90, 3993-4009.  
16546374 J.J.Gray (2006).
High-resolution protein-protein docking.
  Curr Opin Struct Biol, 16, 183-193.  
16842869 J.Macdonald, Z.Li, W.Su, and L.J.Pike (2006).
The membrane proximal disulfides of the EGF receptor extracellular domain are required for high affinity binding and signal transduction but do not play a role in the localization of the receptor to lipid rafts.
  Biochim Biophys Acta, 1763, 870-878.  
16267617 J.N.Contessa, A.Abell, R.B.Mikkelsen, K.Valerie, and R.K.Schmidt-Ullrich (2006).
Compensatory ErbB3/c-Src signaling enhances carcinoma cell survival to ionizing radiation.
  Breast Cancer Res Treat, 95, 17-27.  
17026767 R.A.Stein, and J.V.Staros (2006).
Insights into the evolution of the ErbB receptor family and their ligands from sequence analysis.
  BMC Evol Biol, 6, 79.  
16380971 S.Aifa, N.Miled, F.Frikha, M.R.Aniba, S.P.Svensson, and A.Rebai (2006).
Electrostatic interactions of peptides flanking the tyrosine kinase domain in the epidermal growth factor receptor provides a model for intracellular dimerization and autophosphorylation.
  Proteins, 62, 1036-1043.  
16788977 S.Kamath, and J.K.Buolamwini (2006).
Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development.
  Med Res Rev, 26, 569-594.  
17032651 S.P.van der Woning, W.van Rotterdam, S.B.Nabuurs, H.Venselaar, S.Jacobs-Oomen, M.Wingens, G.Vriend, C.Stortelers, and E.J.van Zoelen (2006).
Negative constraints underlie the ErbB specificity of epidermal growth factor-like ligands.
  J Biol Chem, 281, 40033-40040.  
16889899 S.Sebastian, J.Settleman, S.J.Reshkin, A.Azzariti, A.Bellizzi, and A.Paradiso (2006).
The complexity of targeting EGFR signalling in cancer: from expression to turnover.
  Biochim Biophys Acta, 1766, 120-139.  
16624867 V.P.Ramsauer, V.Pino, A.Farooq, C.A.Carothers Carraway, P.J.Salas, and K.L.Carraway (2006).
Muc4-ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells indicate that Muc4 acts as an unorthodox ligand for ErbB2.
  Mol Biol Cell, 17, 2931-2941.  
16732286 W.A.Barton, D.Tzvetkova-Robev, E.P.Miranda, M.V.Kolev, K.R.Rajashankar, J.P.Himanen, and D.B.Nikolov (2006).
Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
  Nat Struct Mol Biol, 13, 524-532.
PDB codes: 2gy5 2gy7
16777603 X.Zhang, J.Gureasko, K.Shen, P.A.Cole, and J.Kuriyan (2006).
An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor.
  Cell, 125, 1137-1149.
PDB codes: 2gs2 2gs6 2gs7
16355407 Y.S.Kim, R.Bhandari, J.R.Cochran, J.Kuriyan, and K.D.Wittrup (2006).
Directed evolution of the epidermal growth factor receptor extracellular domain for expression in yeast.
  Proteins, 62, 1026-1035.  
16946702 Y.Teramura, J.Ichinose, H.Takagi, K.Nishida, T.Yanagida, and Y.Sako (2006).
Single-molecule analysis of epidermal growth factor binding on the surface of living cells.
  EMBO J, 25, 4215-4222.  
15994331 A.H.Clayton, F.Walker, S.G.Orchard, C.Henderson, D.Fuchs, J.Rothacker, E.C.Nice, and A.W.Burgess (2005).
Ligand-induced dimer-tetramer transition during the activation of the cell surface epidermal growth factor receptor-A multidimensional microscopy analysis.
  J Biol Chem, 280, 30392-30399.  
15795223 A.N.Weber, M.C.Moncrieffe, M.Gangloff, J.L.Imler, and N.J.Gay (2005).
Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway.
  J Biol Chem, 280, 22793-22799.  
16555995 A.P.Majumdar (2005).
Therapeutic potential of EGFR-related protein, a universal EGFR family antagonist.
  Future Oncol, 1, 235-245.  
15611079 B.S.Kochupurakkal, D.Harari, A.Di-Segni, G.Maik-Rachline, L.Lyass, G.Gur, G.Kerber, A.Citri, S.Lavi, R.Eilam, V.Chalifa-Caspi, Z.Eshhar, E.Pikarsky, R.Pinkas-Kramarski, S.S.Bacus, and Y.Yarden (2005).
Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity.
  J Biol Chem, 280, 8503-8512.  
16207817 C.Haslekås, K.Breen, K.W.Pedersen, L.E.Johannessen, E.Stang, and I.H.Madshus (2005).
The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane.
  Mol Biol Cell, 16, 5832-5842.  
15688065 C.P.Blobel (2005).
ADAMs: key components in EGFR signalling and development.
  Nat Rev Mol Cell Biol, 6, 32-43.  
16103229 D.S.Lidke, K.A.Lidke, B.Rieger, T.M.Jovin, and D.J.Arndt-Jovin (2005).
Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors.
  J Cell Biol, 170, 619-626.  
16212492 G.Vert, J.L.Nemhauser, N.Geldner, F.Hong, and J.Chory (2005).
Molecular mechanisms of steroid hormone signaling in plants.
  Annu Rev Cell Dev Biol, 21, 177-201.  
15829568 J.Dong, L.K.Opresko, W.Chrisler, G.Orr, R.D.Quesenberry, D.A.Lauffenburger, and H.S.Wiley (2005).
The membrane-anchoring domain of epidermal growth factor receptor ligands dictates their ability to operate in juxtacrine mode.
  Mol Biol Cell, 16, 2984-2998.  
16107719 J.P.Dawson, M.B.Berger, C.C.Lin, J.Schlessinger, M.A.Lemmon, and K.M.Ferguson (2005).
Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface.
  Mol Cell Biol, 25, 7734-7742.  
15840573 K.Choowongkomon, C.R.Carlin, and F.D.Sönnichsen (2005).
A structural model for the membrane-bound form of the juxtamembrane domain of the epidermal growth factor receptor.
  J Biol Chem, 280, 24043-24052.
PDB code: 1z9i
15611073 K.Kani, C.M.Warren, C.S.Kaddis, J.A.Loo, and R.Landgraf (2005).
Oligomers of ERBB3 have two distinct interfaces that differ in their sensitivity to disruption by heregulin.
  J Biol Chem, 280, 8238-8247.  
15480783 M.J.Oliveira, T.Lauwaet, G.De Bruyne, M.Mareel, and A.Leroy (2005).
Listeria monocytogenes produces a pro-invasive factor that signals via ErbB2/ErbB3 heterodimers.
  J Cancer Res Clin Oncol, 131, 49-59.  
15864276 N.E.Hynes, and H.A.Lane (2005).
ERBB receptors and cancer: the complexity of targeted inhibitors.
  Nat Rev Cancer, 5, 341-354.  
15660449 P.Aller, L.Voiry, N.Garnier, and M.Genest (2005).
Molecular dynamics (MD) investigations of preformed structures of the transmembrane domain of the oncogenic Neu receptor dimer in a DMPC bilayer.
  Biopolymers, 77, 184-197.  
15596490 P.Bagossi, G.Horváth, G.Vereb, J.Szöllösi, and J.Tözsér (2005).
Molecular modeling of nearly full-length ErbB2 receptor.
  Biophys J, 88, 1354-1363.  
15920761 P.Hu, J.Feng, T.Zhou, J.Wang, B.Jing, M.Yu, M.Hu, X.Zhang, B.Shen, and N.Guo (2005).
In vivo identification of the interaction site of ErbB2 extracellular domain with its autoinhibitor.
  J Cell Physiol, 205, 335-343.  
16113650 Q.Wang, G.Villeneuve, and Z.Wang (2005).
Control of epidermal growth factor receptor endocytosis by receptor dimerization, rather than receptor kinase activation.
  EMBO Rep, 6, 942-948.  
16203964 S.Bouyain, P.A.Longo, S.Li, K.M.Ferguson, and D.J.Leahy (2005).
The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand.
  Proc Natl Acad Sci U S A, 102, 15024-15029.
PDB code: 2ahx
15837620 S.Li, K.R.Schmitz, P.D.Jeffrey, J.J.Wiltzius, P.Kussie, and K.M.Ferguson (2005).
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.
  Cancer Cell, 7, 301-311.
PDB codes: 1yy8 1yy9
16338790 S.S.Hobbs, R.M.Gallo, and D.J.Riese (2005).
Phe45 of NRG2beta is critical for the affinity of NRG2beta for ErbB4 and for potent stimulation of ErbB4 signaling by NRG2beta*.
  Growth Factors, 23, 273-283.  
15749770 T.Uyemura, H.Takagi, T.Yanagida, and Y.Sako (2005).
Single-molecule analysis of epidermal growth factor signaling that leads to ultrasensitive calcium response.
  Biophys J, 88, 3720-3730.  
15094157 A.Bennasroune, A.Gardin, D.Aunis, G.Crémel, and P.Hubert (2004).
Tyrosine kinase receptors as attractive targets of cancer therapy.
  Crit Rev Oncol Hematol, 50, 23-38.  
15122207 A.Gschwind, O.M.Fischer, and A.Ullrich (2004).
The discovery of receptor tyrosine kinases: targets for cancer therapy.
  Nat Rev Cancer, 4, 361-370.  
15166146 D.Alvarado, A.H.Rice, and J.B.Duffy (2004).
Bipartite inhibition of Drosophila epidermal growth factor receptor by the extracellular and transmembrane domains of Kekkon1.
  Genetics, 167, 187-202.  
14732693 D.Mattoon, P.Klein, M.A.Lemmon, I.Lax, and J.Schlessinger (2004).
The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor function.
  Proc Natl Acad Sci U S A, 101, 923-928.  
15016810 F.Walker, S.G.Orchard, R.N.Jorissen, N.E.Hall, H.H.Zhang, P.A.Hoyne, T.E.Adams, T.G.Johns, C.Ward, T.P.Garrett, H.J.Zhu, M.Nerrie, A.M.Scott, E.C.Nice, and A.W.Burgess (2004).
CR1/CR2 interactions modulate the functions of the cell surface epidermal growth factor receptor.
  J Biol Chem, 279, 22387-22398.  
14748658 G.M.Higa (2004).
Targeted therapies in oncology: in the crosshairs or at the crossroads?
  Expert Rev Anticancer Ther, 4, 61-75.  
15606339 G.M.Higa (2004).
Signaling multiplex of the epidermal growth factor receptor.
  Expert Rev Anticancer Ther, 4, 1145-1156.  
15049825 M.Banerjee, J.Copp, D.Vuga, M.Marino, T.Chapman, P.van der Geer, and P.Ghosh (2004).
GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.
  Mol Microbiol, 52, 257-271.  
15093539 M.C.Franklin, K.D.Carey, F.F.Vajdos, D.J.Leahy, Vos, and M.X.Sliwkowski (2004).
Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex.
  Cancer Cell, 5, 317-328.
PDB code: 1s78
15070899 M.Kim, H.Yang, S.K.Kim, P.A.Reche, R.S.Tirabassi, R.E.Hussey, Y.Chishti, J.G.Rheinwald, T.J.Morehead, T.Zech, I.K.Damon, R.M.Welsh, and E.L.Reinherz (2004).
Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies.
  J Biol Chem, 279, 25838-25848.  
14732694 P.Klein, D.Mattoon, M.A.Lemmon, and J.Schlessinger (2004).
A structure-based model for ligand binding and dimerization of EGF receptors.
  Proc Natl Acad Sci U S A, 101, 929-934.  
15331606 R.Takazaki, Y.Shishido, R.Iwamoto, and E.Mekada (2004).
Suppression of the biological activities of the epidermal growth factor (EGF)-like domain by the heparin-binding domain of heparin-binding EGF-like Growth Factor.
  J Biol Chem, 279, 47335-47343.  
15516922 S.Otte, and C.Barlowe (2004).
Sorting signals can direct receptor-mediated export of soluble proteins into COPII vesicles.
  Nat Cell Biol, 6, 1189-1194.  
15238521 T.Donaldson, S.H.Wang, T.L.Jacobsen, B.Schnepp, J.Price, and A.Simcox (2004).
Regulation of the Drosophila epidermal growth factor-ligand vein is mediated by multiple domains.
  Genetics, 167, 687-698.  
15075331 T.G.Johns, T.E.Adams, J.R.Cochran, N.E.Hall, P.A.Hoyne, M.J.Olsen, Y.S.Kim, J.Rothacker, E.C.Nice, F.Walker, G.Ritter, A.A.Jungbluth, L.J.Old, C.W.Ward, A.W.Burgess, K.D.Wittrup, and A.M.Scott (2004).
Identification of the epitope for the epidermal growth factor receptor-specific monoclonal antibody 806 reveals that it preferentially recognizes an untethered form of the receptor.
  J Biol Chem, 279, 30375-30384.  
14744244 T.Holbro, and N.E.Hynes (2004).
ErbB receptors: directing key signaling networks throughout life.
  Annu Rev Pharmacol Toxicol, 44, 195-217.  
15194811 X.Yin, N.J.Gower, H.A.Baylis, and K.Strange (2004).
Inositol 1,4,5-trisphosphate signaling regulates rhythmic contractile activity of myoepithelial sheath cells in Caenorhabditis elegans.
  Mol Biol Cell, 15, 3938-3949.  
15231819 Y.X.Fan, L.Wong, T.B.Deb, and G.R.Johnson (2004).
Ligand regulates epidermal growth factor receptor kinase specificity: activation increases preference for GAB1 and SHC versus autophosphorylation sites.
  J Biol Chem, 279, 38143-38150.  
12819119 A.D.Alexander, F.Villalta, and M.F.Lima (2003).
Transforming growth factor alpha binds to Trypanosoma cruzi amastigotes to induce signaling and cellular proliferation.
  Infect Immun, 71, 4201-4205.  
14527402 A.W.Burgess, H.S.Cho, C.Eigenbrot, K.M.Ferguson, T.P.Garrett, D.J.Leahy, M.A.Lemmon, M.X.Sliwkowski, C.W.Ward, and S.Yokoyama (2003).
An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors.
  Mol Cell, 12, 541-552.  
12614348 B.Malissen (2003).
An evolutionary and structural perspective on T cell antigen receptor function.
  Immunol Rev, 191, 7.  
12734179 C.Couturier, and R.Jockers (2003).
Activation of the leptin receptor by a ligand-induced conformational change of constitutive receptor dimers.
  J Biol Chem, 278, 26604-26611.  
12556529 C.Stortelers, S.P.van der Woning, S.Jacobs-Oomen, M.Wingens, and E.J.van Zoelen (2003).
Selective formation of ErbB-2/ErbB-3 heterodimers depends on the ErbB-3 affinity of epidermal growth factor-like ligands.
  J Biol Chem, 278, 12055-12063.  
14632199 C.Stove, V.Stove, L.Derycke, V.Van Marck, M.Mareel, and M.Bracke (2003).
The heregulin/human epidermal growth factor receptor as a new growth factor system in melanoma with multiple ways of deregulation.
  J Invest Dermatol, 121, 802-812.  
14528000 E.Gherardi, M.E.Youles, R.N.Miguel, T.L.Blundell, L.Iamele, J.Gough, A.Bandyopadhyay, G.Hartmann, and P.J.Butler (2003).
Functional map and domain structure of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor.
  Proc Natl Acad Sci U S A, 100, 12039-12044.  
14530278 E.J.Westover, D.F.Covey, H.L.Brockman, R.E.Brown, and L.J.Pike (2003).
Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects. Studies with cholesterol enantiomers.
  J Biol Chem, 278, 51125-51133.  
12707299 F.Lühder, Y.Huang, K.M.Dennehy, C.Guntermann, I.Müller, E.Winkler, T.Kerkau, S.Ikemizu, S.J.Davis, T.Hanke, and T.Hünig (2003).
Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists.
  J Exp Med, 197, 955-966.  
14675545 G.Rudenko, and J.Deisenhofer (2003).
The low-density lipoprotein receptor: ligands, debates and lore.
  Curr Opin Struct Biol, 13, 683-689.  
12610629 H.S.Cho, K.Mason, K.X.Ramyar, A.M.Stanley, S.B.Gabelli, D.W.Denney, and D.J.Leahy (2003).
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.
  Nature, 421, 756-760.
PDB codes: 1n8y 1n8z
  12813928 H.S.Earp, B.F.Calvo, and C.I.Sartor (2003).
The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4.
  Trans Am Clin Climatol Assoc, 114, 315.  
12667445 J.Greenwald, J.Groppe, P.Gray, E.Wiater, W.Kwiatkowski, W.Vale, and S.Choe (2003).
The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
  Mol Cell, 11, 605-617.
PDB codes: 1lx5 1lxi
12620237 K.M.Ferguson, M.B.Berger, J.M.Mendrola, H.S.Cho, D.J.Leahy, and M.A.Lemmon (2003).
EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization.
  Mol Cell, 11, 507-517.
PDB code: 1nql
12791136 M.P.Machner, S.Frese, W.D.Schubert, V.Orian-Rousseau, E.Gherardi, J.Wehland, H.H.Niemann, and D.W.Heinz (2003).
Aromatic amino acids at the surface of InlB are essential for host cell invasion by Listeria monocytogenes.
  Mol Microbiol, 48, 1525-1536.  
12869697 M.Sagermann, L.Gay, and B.W.Matthews (2003).
Long-distance conformational changes in a protein engineered by modulated sequence duplication.
  Proc Natl Acad Sci U S A, 100, 9191-9195.
PDB code: 1oyu
12869572 M.Wingens, T.Walma, H.van Ingen, C.Stortelers, J.E.van Leeuwen, E.J.van Zoelen, and G.W.Vuister (2003).
Structural analysis of an epidermal growth factor/transforming growth factor-alpha chimera with unique ErbB binding specificity.
  J Biol Chem, 278, 39114-39123.
PDB code: 1p9j
12605220 M.X.Sliwkowski (2003).
Ready to partner.
  Nat Struct Biol, 10, 158-159.  
12620236 T.P.Garrett, N.M.McKern, M.Lou, T.C.Elleman, T.E.Adams, G.O.Lovrecz, M.Kofler, R.N.Jorissen, E.C.Nice, A.W.Burgess, and C.W.Ward (2003).
The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors.
  Mol Cell, 11, 495-505.
PDB code: 2a91
14708119 W.S.Hlavacek, J.R.Faeder, M.L.Blinov, A.S.Perelson, and B.Goldstein (2003).
The complexity of complexes in signal transduction.
  Biotechnol Bioeng, 84, 783-794.  
12731890 Y.Zhen, R.M.Caprioli, and J.V.Staros (2003).
Characterization of glycosylation sites of the epidermal growth factor receptor.
  Biochemistry, 42, 5478-5492.  
12297050 H.Ogiso, R.Ishitani, O.Nureki, S.Fukai, M.Yamanaka, J.H.Kim, K.Saito, A.Sakamoto, M.Inoue, M.Shirouzu, and S.Yokoyama (2002).
Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains.
  Cell, 110, 775-787.
PDB code: 1ivo
12196540 J.Stamos, M.X.Sliwkowski, and C.Eigenbrot (2002).
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
  J Biol Chem, 277, 46265-46272.
PDB codes: 1m14 1m17
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