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PDBsum entry 1n8y
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Transferase PDB id
1n8y

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
592 a.a. *
Ligands
NAG-NAG ×2
NAG
Waters ×84
* Residue conservation analysis
PDB id:
1n8y
Name: Transferase
Title: Crystal structure of the extracellular region of rat her2
Structure: Protooncoprotein. Chain: c. Fragment: extracellular region (residues 26-633). Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: neu. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.
Resolution:
2.40Å     R-factor:   0.224     R-free:   0.282
Authors: H.-S.Cho,K.Mason,K.X.Ramyar,A.M.Stanley,S.B.Gabelli,D.W.Denney Jr., D.J.Leahy
Key ref:
H.S.Cho et al. (2003). Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature, 421, 756-760. PubMed id: 12610629 DOI: 10.1038/nature01392
Date:
21-Nov-02     Release date:   18-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06494  (ERBB2_RAT) -  Receptor tyrosine-protein kinase erbB-2 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1257 a.a.
592 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
L-tyrosyl-[protein]
 + ATP
 = O-phospho-L-tyrosyl-[protein]
Bound ligand (Het Group name = NAG)
matches with 41.38% similarity 		+ ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1038/nature01392 Nature 421:756-760 (2003)
PubMed id: 12610629  
 
 
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab.
H.S.Cho, K.Mason, K.X.Ramyar, A.M.Stanley, S.B.Gabelli, D.W.Denney, D.J.Leahy.
 
  ABSTRACT  
 
HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: The structure of rat and human sHER2. a, Ribbon diagram of rat sHER2. Domains I (blue), II (green), III (yellow) and IV (red), and the amino and carboxy termini, are indicated. Disulphide bonds are shown in purple and gold. b, Ribbon diagram of the human sHER2 (coloured as in a) and Herceptin Fab (cyan) complex. Figures 1 and 2c were made using the program Ribbons29. 		Figure 3.
Figure 3: Relationship of sHER2 to ligand-activated sHER1. Orthogonal views of sHER2 (green) and sHER1 (blue) with EGF (red) bound^10 after superposition of domain III. Domain II has been omitted from the figure on the left for clarity.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2003, 421, 756-760) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22785351 Y.Yarden, and G.Pines (2012).
The ERBB network: at last, cancer therapy meets systems biology.
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21288302 F.Troise, M.Monti, A.Merlino, F.Cozzolino, C.Fedele, I.R.Krauss, F.Sica, P.Pucci, G.D'Alessio, and C.De Lorenzo (2011).
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20684884 M.Campone, P.Juin, F.André, and T.Bachelot (2011).
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20589763 A.B.Pfister, R.C.Wood, P.J.Salas, D.L.Zea, and V.P.Ramsauer (2010).
Early response to ErbB2 over-expression in polarized Caco-2 cells involves partial segregation from ErbB3 by relocalization to the apical surface and initiation of survival signaling.
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Anti-HER-2 engineering antibody ChA21 inhibits growth and induces apoptosis of SK-OV-3 cells.
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20696930 C.Eigenbrot, M.Ultsch, A.Dubnovitsky, L.Abrahmsén, and T.Härd (2010).
Structural basis for high-affinity HER2 receptor binding by an engineered protein.
  Proc Natl Acad Sci U S A, 107, 15039-15044.
PDB codes: 2kzi 2kzj 3mzw
20836684 G.M.Higa, V.Singh, and J.Abraham (2010).
Biological considerations and clinical applications of new HER2-targeted agents.
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20960451 H.Chen, G.Pimienta, Y.Gu, X.Sun, J.Hu, M.S.Kim, R.Chaerkady, M.Gucek, R.N.Cole, S.Sukumar, and A.Pandey (2010).
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Structural basis of immunosuppression by the therapeutic antibody daclizumab.
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PDB codes: 3nfp 3nfs
20943641 J.Baselga (2010).
Treatment of HER2-overexpressing breast cancer.
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20432069 J.H.Bae, and J.Schlessinger (2010).
Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinases.
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20022944 J.Monsey, W.Shen, P.Schlesinger, and R.Bose (2010).
Her4 and Her2/neu tyrosine kinase domains dimerize and activate in a reconstituted in vitro system.
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21119106 L.Chen, J.Placone, L.Novicky, and K.Hristova (2010).
The extracellular domain of fibroblast growth factor receptor 3 inhibits ligand-independent dimerization.
  Sci Signal, 3, ra86.  
20870669 L.Tookman, and R.Roylance (2010).
New drugs for breast cancer.
  Br Med Bull, 96, 111-129.  
21203579 M.Gijsen, P.King, T.Perera, P.J.Parker, A.L.Harris, B.Larijani, and A.Kong (2010).
HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer.
  PLoS Biol, 8, e1000563.  
20021208 M.Hollmén, and K.Elenius (2010).
Potential of ErbB4 antibodies for cancer therapy.
  Future Oncol, 6, 37-53.  
20021303 M.K.Lee, A.Sharma, and B.J.Czerniecki (2010).
It's all in for the HER family in tumorigenesis.
  Expert Rev Vaccines, 9, 29-34.  
20532501 M.Z.Ladjemi, W.Jacot, T.Chardès, A.Pèlegrin, and I.Navarro-Teulon (2010).
Anti-HER2 vaccines: new prospects for breast cancer therapy.
  Cancer Immunol Immunother, 59, 1295-1312.  
20813958 P.Nagy, J.Claus, T.M.Jovin, and D.J.Arndt-Jovin (2010).
Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis.
  Proc Natl Acad Sci U S A, 107, 16524-16529.  
20933094 P.Sanchez-Soria, and T.D.Camenisch (2010).
ErbB signaling in cardiac development and disease.
  Semin Cell Dev Biol, 21, 929-935.  
20677900 R.Dhankhar, S.P.Vyas, A.K.Jain, S.Arora, G.Rath, and A.K.Goyal (2010).
Advances in novel drug delivery strategies for breast cancer therapy.
  Artif Cells Blood Substit Immobil Biotechnol, 38, 230-249.  
19859802 R.Dua, J.Zhang, P.Nhonthachit, E.Penuel, C.Petropoulos, and G.Parry (2010).
EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance.
  Breast Cancer Res Treat, 122, 685-697.  
20383388 S.Birtalan, R.D.Fisher, and S.S.Sidhu (2010).
The functional capacity of the natural amino acids for molecular recognition.
  Mol Biosyst, 6, 1186-1194.  
20125090 S.Di Cosimo, and J.Baselga (2010).
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  Nat Rev Clin Oncol, 7, 139-147.  
19624808 A.Sassen, S.Diermeier-Daucher, M.Sieben, O.Ortmann, F.Hofstaedter, S.Schwarz, and G.Brockhoff (2009).
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  Breast Cancer Res, 11, R50.  
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
19748186 D.Collins, A.D.Hill, and L.Young (2009).
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  21160542 J.Barth, C.Jackisch, and M.Untch (2009).
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  Science, 323, 1610-1614.
PDB codes: 3bdy 3be1
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18992239 K.R.Schmitz, and K.M.Ferguson (2009).
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  Exp Cell Res, 315, 659-670.  
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19296866 L.N.Johnson (2009).
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  Q Rev Biophys, 42, 1.  
19038249 M.A.Lemmon (2009).
Ligand-induced ErbB receptor dimerization.
  Exp Cell Res, 315, 638-648.  
19151766 M.Hollmén, J.A.Määttä, L.Bald, M.X.Sliwkowski, and K.Elenius (2009).
Suppression of breast cancer cell growth by a monoclonal antibody targeting cleavable ErbB4 isoforms.
  Oncogene, 28, 1309-1319.  
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.
  Biomark Med, 3, 139-151.  
19017278 N.Zeng, L.Liu, M.G.McCabe, D.T.Jones, K.Ichimura, and V.P.Collins (2009).
Real-time quantitative polymerase chain reaction (qPCR) analysis with fluorescence resonance energy transfer (FRET) probes reveals differential expression of the four ERBB4 juxtamembrane region variants between medulloblastoma and pilocytic astrocytoma.
  Neuropathol Appl Neurobiol, 35, 353-366.  
  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.
  Mol Med, 15, 11-20.  
19664181 P.K.Morrow, F.Zambrana, and F.J.Esteva (2009).
Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer.
  Breast Cancer Res, 11, 207.  
18941743 P.Karagiannis, J.Singer, J.Hunt, S.K.Gan, S.M.Rudman, D.Mechtcheriakova, R.Knittelfelder, T.R.Daniels, P.S.Hobson, A.J.Beavil, J.Spicer, F.O.Nestle, M.L.Penichet, H.J.Gould, E.Jensen-Jarolim, and S.N.Karagiannis (2009).
Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells.
  Cancer Immunol Immunother, 58, 915-930.  
19752336 P.T.Kaumaya, K.C.Foy, J.Garrett, S.V.Rawale, D.Vicari, J.M.Thurmond, T.Lamb, A.Mani, Y.Kane, C.R.Balint, D.Chalupa, G.A.Otterson, C.L.Shapiro, J.M.Fowler, M.R.Grever, T.S.Bekaii-Saab, and W.E.Carson (2009).
Phase I active immunotherapy with combination of two chimeric, human epidermal growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope in patients with metastatic and/or recurrent solid tumors.
  J Clin Oncol, 27, 5270-5277.  
18761339 R.Bose, and X.Zhang (2009).
The ErbB kinase domain: structural perspectives into kinase activation and inhibition.
  Exp Cell Res, 315, 649-658.  
19344285 R.Knittelfelder, A.B.Riemer, and E.Jensen-Jarolim (2009).
Mimotope vaccination--from allergy to cancer.
  Expert Opin Biol Ther, 9, 493-506.  
19289058 S.E.Telesco, and R.Radhakrishnan (2009).
Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.
  Biophys J, 96, 2321-2334.  
19188134 S.Gori, A.Sidoni, M.Colozza, I.Ferri, M.G.Mameli, D.Fenocchio, L.Stocchi, J.Foglietta, V.Ludovini, E.Minenza, V.De Angelis, and L.Crinò (2009).
EGFR, pMAPK, pAkt and PTEN status by immunohistochemistry: correlation with clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab.
  Ann Oncol, 20, 648-654.  
19376231 S.O'Connor, E.Li, B.S.Majors, L.He, J.Placone, D.Baycin, M.J.Betenbaugh, and K.Hristova (2009).
Increased expression of the integral membrane protein ErbB2 in Chinese hamster ovary cells expressing the anti-apoptotic gene Bcl-xL.
  Protein Expr Purif, 67, 41-47.  
  20140073 S.S.Negi, and W.Braun (2009).
Automated detection of conformational epitopes using phage display Peptide sequences.
  Bioinform Biol Insights, 3, 71-81.  
19703026 S.Satyanarayanajois, S.Villalba, L.Jianchao, and G.M.Lin (2009).
Design, synthesis, and docking studies of peptidomimetics based on HER2-herceptin binding site with potential antiproliferative activity against breast cancer cell lines.
  Chem Biol Drug Des, 74, 246-257.  
  20065649 X.Wang, T.K.Das, S.K.Singh, and S.Kumar (2009).
Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies.
  MAbs, 1, 254-267.  
19221151 Y.H.Choi, J.H.Ahn, S.B.Kim, K.H.Jung, G.Y.Gong, M.J.Kim, B.H.Son, S.H.Ahn, and W.K.Kim (2009).
Tissue microarray-based study of patients with lymph node-negative breast cancer shows that HER2/neu overexpression is an important predictive marker of poor prognosis.
  Ann Oncol, 20, 1337-1343.  
19190626 Y.Xu, N.Benlimame, J.Su, Q.He, and M.A.Alaoui-Jamali (2009).
Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells.
  Br J Cancer, 100, 633-643.  
19717564 Z.Ma, Q.Li, H.An, M.S.Pankonin, J.Wang, and J.A.Loeb (2009).
Targeting human epidermal growth factor receptor signaling with the neuregulin's heparin-binding domain.
  J Biol Chem, 284, 32108-32115.  
18829509 C.L.Arteaga, A.O'Neill, S.L.Moulder, M.Pins, J.A.Sparano, G.W.Sledge, and N.E.Davidson (2008).
A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer.
  Clin Cancer Res, 14, 6277-6283.  
18334220 C.Qiu, M.K.Tarrant, S.H.Choi, A.Sathyamurthy, R.Bose, S.Banjade, A.Pal, W.G.Bornmann, M.A.Lemmon, P.A.Cole, and D.J.Leahy (2008).
Mechanism of activation and inhibition of the HER4/ErbB4 kinase.
  Structure, 16, 460-467.
PDB codes: 3bbt 3bbw 3bce
18394550 D.J.Leahy (2008).
A molecular view of anti-ErbB monoclonal antibody therapy.
  Cancer Cell, 13, 291-293.  
18798529 G.K.Dy, and A.A.Adjei (2008).
Systemic cancer therapy: evolution over the last 60 years.
  Cancer, 113, 1857-1887.  
19046108 G.Tomasello, E.de Azambuja, P.Dinh, N.Snoj, and M.Piccart-Gebhart (2008).
Jumping higher: is it still possible? The ALTTO trial challenge.
  Expert Rev Anticancer Ther, 8, 1883-1890.  
18411193 I.G.Muñoz, F.J.Blanco, and G.Montoya (2008).
On the relevance of defining protein structures in cancer research.
  Clin Transl Oncol, 10, 204-212.  
18366039 J.Gao, Y.G.Liu, R.Liu, and R.A.Zingaro (2008).
Herceptin-platinum(II) binding complexes: novel cancer-cell-specific agents.
  ChemMedChem, 3, 954-962.  
18165319 J.L.Macdonald, and L.J.Pike (2008).
Heterogeneity in EGF-binding affinities arises from negative cooperativity in an aggregating system.
  Proc Natl Acad Sci U S A, 105, 112-117.  
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
18573086 K.M.Ferguson (2008).
Structure-based view of epidermal growth factor receptor regulation.
  Annu Rev Biophys, 37, 353-373.  
18359855 L.Berglund, J.Andrade, J.Odeberg, and M.Uhlén (2008).
The epitope space of the human proteome.
  Protein Sci, 17, 606-613.  
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.
  J Biol Chem, 283, 14629-14635.  
18454161 M.Hermes, W.Schormann, M.Brulport, K.Uhlemann, F.Lupatsch, L.C.Horn, A.Schumann, C.Allgaier, M.Weishaupt, K.Engeland, G.A.Müller, J.Mössner, A.Bauer, I.B.Schiffer, S.Gebhard, M.Schmidt, E.Lausch, D.Prawitt, C.Wilhelm, and J.G.Hengstler (2008).
Trastuzumab therapy vs tetracycline controlled ERBB2 downregulation: influence on tumour development in an ERBB2-dependent mouse tumour model.
  Br J Cancer, 98, 1525-1532.  
18259690 M.J.Wieduwilt, and M.M.Moasser (2008).
The epidermal growth factor receptor family: biology driving targeted therapeutics.
  Cell Mol Life Sci, 65, 1566-1584.  
18031935 M.Landau, and N.Ben-Tal (2008).
Dynamic equilibrium between multiple active and inactive conformations explains regulation and oncogenic mutations in ErbB receptors.
  Biochim Biophys Acta, 1785, 12-31.  
18613764 M.P.Deonarain (2008).
Recombinant antibodies for cancer therapy.
  Expert Opin Biol Ther, 8, 1123-1141.  
18585454 M.Peipp, M.Dechant, and T.Valerius (2008).
Effector mechanisms of therapeutic antibodies against ErbB receptors.
  Curr Opin Immunol, 20, 436-443.  
18679398 O.N.Ikediobi (2008).
Somatic pharmacogenomics in cancer.
  Pharmacogenomics J, 8, 305-314.  
18045863 P.A.Barthelemy, H.Raab, B.A.Appleton, C.J.Bond, P.Wu, C.Wiesmann, and S.S.Sidhu (2008).
Comprehensive Analysis of the Factors Contributing to the Stability and Solubility of Autonomous Human VH Domains.
  J Biol Chem, 283, 3639-3654.
PDB code: 3b9v
18230610 P.Cironi, I.A.Swinburne, and P.A.Silver (2008).
Enhancement of cell type specificity by quantitative modulation of a chimeric ligand.
  J Biol Chem, 283, 8469-8476.  
18803451 P.H.Tan, and A.S.Lota (2008).
Interaction of current cancer treatments and the immune system: implications for breast cancer therapeutics.
  Expert Opin Pharmacother, 9, 2639-2660.  
17721938 R.M.Ionescu, J.Vlasak, C.Price, and M.Kirchmeier (2008).
Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies.
  J Pharm Sci, 97, 1414-1426.  
20686639 R.Shukla, T.P.Thomas, A.M.Desai, A.Kotlyar, S.J.Park, and J.R.Baker (2008).
HER2 specific Delivery of Methotrexate by Dendrimer Conjugated anti-HER2 mAb.
  Nanotechnology, 19, 295102.  
18596360 S.Diermeier-Daucher, M.Hasmann, and G.Brockhoff (2008).
Flow cytometric FRET analysis of erbB receptor interaction on a cell-by-cell basis.
  Ann N Y Acad Sci, 1130, 280-286.  
17847085 S.Hu, Z.Zhu, L.Li, L.Chang, W.Li, L.Cheng, M.Teng, and J.Liu (2008).
Epitope mapping and structural analysis of an anti-ErbB2 antibody A21: Molecular basis for tumor inhibitory mechanism.
  Proteins, 70, 938-949.
PDB code: 2gjj
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
18269312 S.Rolla, C.Marchini, S.Malinarich, E.Quaglino, S.Lanzardo, M.Montani, M.Iezzi, M.Angeletti, G.Ramadori, G.Forni, F.Cavallo, and A.Amici (2008).
Protective immunity against neu-positive carcinomas elicited by electroporation of plasmids encoding decreasing fragments of rat neu extracellular domain.
  Hum Gene Ther, 19, 229-240.  
  18795122 T.Negri, E.Tamborini, G.P.Dagrada, A.Greco, S.Staurengo, M.Guzzo, L.D.Locati, A.Carbone, M.A.Pierotti, L.Licitra, and S.Pilotti (2008).
TRK-A, HER-2/neu, and KIT Expression/Activation Profiles in Salivary Gland Carcinoma.
  Transl Oncol, 1, 121-128.  
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.  
18264138 Z.Cai, G.Zhang, Z.Zhou, K.Bembas, J.A.Drebin, M.I.Greene, and H.Zhang (2008).
Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.
  Oncogene, 27, 3870-3874.  
17154432 A.K.Hirsch, F.R.Fischer, and F.Diederich (2007).
Phosphate recognition in structural biology.
  Angew Chem Int Ed Engl, 46, 338-352.  
17525746 C.Ginestier, J.Adélaïde, A.Gonçalvès, L.Repellini, F.Sircoulomb, A.Letessier, P.Finetti, J.Geneix, E.Charafe-Jauffret, F.Bertucci, J.Jacquemier, P.Viens, and D.Birnbaum (2007).
ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines.
  Oncogene, 26, 7163-7169.  
17624800 C.Magdelaine-Beuzelin, Q.Kaas, V.Wehbi, M.Ohresser, R.Jefferis, M.P.Lefranc, and H.Watier (2007).
Structure-function relationships of the variable domains of monoclonal antibodies approved for cancer treatment.
  Crit Rev Oncol Hematol, 64, 210-225.  
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.  
17288526 D.S.Hirsch, and W.J.Wu (2007).
Cdc42: an effector and regulator of ErbB1 as a strategic target in breast cancer therapy.
  Expert Rev Anticancer Ther, 7, 147-157.  
17427229 E.M.Bublil, N.T.Freund, I.Mayrose, O.Penn, A.Roitburd-Berman, N.D.Rubinstein, T.Pupko, and J.M.Gershoni (2007).
Stepwise prediction of conformational discontinuous B-cell epitopes using the Mapitope algorithm.
  Proteins, 68, 294-304.  
17360519 F.Mancia, S.Brenner-Morton, R.Siegel, Z.Assur, Y.Sun, I.Schieren, M.Mendelsohn, R.Axel, and W.A.Hendrickson (2007).
Production and characterization of monoclonal antibodies sensitive to conformation in the 5HT2c serotonin receptor.
  Proc Natl Acad Sci U S A, 104, 4303-4308.  
17635517 G.Brockhoff, B.Heckel, E.Schmidt-Bruecken, M.Plander, F.Hofstaedter, A.Vollmann, and S.Diermeier (2007).
Differential impact of Cetuximab, Pertuzumab and Trastuzumab on BT474 and SK-BR-3 breast cancer cell proliferation.
  Cell Prolif, 40, 488-507.  
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.  
17697999 J.P.Dawson, Z.Bu, and M.A.Lemmon (2007).
Ligand-induced structural transitions in ErbB receptor extracellular domains.
  Structure, 15, 942-954.  
  17525275 L.Rittié, S.Kansra, S.W.Stoll, Y.Li, J.E.Gudjonsson, Y.Shao, L.E.Michael, G.J.Fisher, T.M.Johnson, and J.T.Elder (2007).
Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin.
  Am J Pathol, 170, 2089-2099.  
17245490 M.Hatakeyama (2007).
System properties of ErbB receptor signaling for the understanding of cancer progression.
  Mol Biosyst, 3, 111-116.  
17471238 M.M.Moasser (2007).
The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis.
  Oncogene, 26, 6469-6487.  
17486079 M.M.Moasser (2007).
Targeting the function of the HER2 oncogene in human cancer therapeutics.
  Oncogene, 26, 6577-6592.  
17979561 M.Persson, I.Sivaev, K.J.Winberg, L.Gedda, P.U.Malmström, and V.Tolmachev (2007).
In vitro evaluation of two polyhedral boron anion derivatives as linkers for attachment of radioiodine to the anti-HER2 monoclonal antibody trastuzumab.
  Cancer Biother Radiopharm, 22, 585-596.  
17716905 N.Congy-Jolivet, A.Probst, H.Watier, and G.Thibault (2007).
Recombinant therapeutic monoclonal antibodies: mechanisms of action in relation to structural and functional duality.
  Crit Rev Oncol Hematol, 64, 226-233.  
17981505 N.V.Sergina, and M.M.Moasser (2007).
The HER family and cancer: emerging molecular mechanisms and therapeutic targets.
  Trends Mol Med, 13, 527-534.  
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.
  Biophys J, 93, 684-698.  
17402790 R.Bartsch, C.Wenzel, C.C.Zielinski, and G.G.Steger (2007).
HER-2-positive breast cancer: hope beyond trastuzumab.
  BioDrugs, 21, 69-77.  
  19707345 R.Bartsch, C.Wenzel, and G.G.Steger (2007).
Trastuzumab in the management of early and advanced stage breast cancer.
  Biologics, 1, 19-31.  
17274834 R.Landgraf (2007).
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks.
  Breast Cancer Res, 9, 202.  
17899385 S.K.Pal, and M.Pegram (2007).
HER2 targeted therapy in breast cancer...beyond Herceptin.
  Rev Endocr Metab Disord, 8, 269-277.  
17043217 A.Negro, B.K.Brar, Y.Gu, K.L.Peterson, W.Vale, and K.F.Lee (2006).
erbB2 is required for G protein-coupled receptor signaling in the heart.
  Proc Natl Acad Sci U S A, 103, 15889-15893.  
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
16983832 B.S.Hendriks, J.Cook, J.M.Burke, J.M.Beusmans, D.A.Lauffenburger, and D.de Graaf (2006).
Computational modelling of ErbB family phosphorylation dynamics in response to transforming growth factor alpha and heregulin indicates spatial compartmentation of phosphatase activity.
  Syst Biol (Stevenage), 153, 22-33.  
16956305 C.Bernard-Marty, F.Lebrun, A.Awada, and M.J.Piccart (2006).
Monoclonal antibody-based targeted therapy in breast cancer: current status and future directions.
  Drugs, 66, 1577-1591.  
16715358 C.M.Ng, B.L.Lum, V.Gimenez, S.Kelsey, and D.Allison (2006).
Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis.
  Pharm Res, 23, 1275-1284.  
16151804 C.W.Adams, D.E.Allison, K.Flagella, L.Presta, J.Clarke, N.Dybdal, K.McKeever, and M.X.Sliwkowski (2006).
Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab.
  Cancer Immunol Immunother, 55, 717-727.  
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.  
16433931 H.T.Chang, T.W.Pai, T.C.Fan, B.H.Su, P.C.Wu, C.Y.Tang, C.T.Chang, S.H.Liu, and M.D.Chang (2006).
A reinforced merging methodology for mapping unique peptide motifs in members of protein families.
  BMC Bioinformatics, 7, 38.  
17088902 H.Yokoyama, Y.Ikehara, Y.Kodera, S.Ikehara, Y.Yatabe, Y.Mochizuki, M.Koike, M.Fujiwara, A.Nakao, M.Tatematsu, and H.Nakanishi (2006).
Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis.
  Br J Cancer, 95, 1504-1513.  
16603068 J.Huang, and W.Honda (2006).
CED: a conformational epitope database.
  BMC Immunol, 7, 7.  
16929325 K.Imai, and A.Takaoka (2006).
Comparing antibody and small-molecule therapies for cancer.
  Nat Rev Cancer, 6, 714-727.  
16311733 M.M.Belimezi, D.Papanastassiou, E.Merkouri, C.N.Baxevanis, and A.Mamalaki (2006).
Growth inhibition of breast cancer cell lines overexpressing Her2/neu by a novel internalized fully human Fab antibody fragment.
  Cancer Immunol Immunother, 55, 1091-1099.  
16843261 N.E.Hynes, and T.Schlange (2006).
Targeting ADAMS and ERBBs in lung cancer.
  Cancer Cell, 10, 7.  
16831078 N.G.Schaefer, B.C.Pestalozzi, A.Knuth, and C.Renner (2006).
Potential use of humanized antibodies in the treatment of breast cancer.
  Expert Rev Anticancer Ther, 6, 1065-1074.  
16917510 N.J.Gay, M.Gangloff, and A.N.Weber (2006).
Toll-like receptors as molecular switches.
  Nat Rev Immunol, 6, 693-698.  
16622479 P.J.Carter (2006).
Potent antibody therapeutics by design.
  Nat Rev Immunol, 6, 343-357.  
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.  
16918262 R.Mehra, and B.Burtness (2006).
Antibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials.
  Expert Opin Biol Ther, 6, 951-962.  
16683005 R.Nahta, D.Yu, M.C.Hung, G.N.Hortobagyi, and F.J.Esteva (2006).
Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer.
  Nat Clin Pract Oncol, 3, 269-280.  
17096862 R.Nahta, and F.J.Esteva (2006).
HER2 therapy: molecular mechanisms of trastuzumab resistance.
  Breast Cancer Res, 8, 215.  
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.  
16963450 S.Kubetzko, E.Balic, R.Waibel, U.Zangemeister-Wittke, and A.Plückthun (2006).
PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment 4D5: effects on tumor targeting.
  J Biol Chem, 281, 35186-35201.  
17393979 S.Selvarajan, K.Y.Wong, K.S.Khoo, B.H.Bay, and P.H.Tan (2006).
Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women.
  Pathology, 38, 528-533.  
16916720 S.Selvarajan, S.Y.Tan, L.H.Sii, and P.H.Tan (2006).
c-erbB-2 (HER-2/neu) immunohistochemistry in invasive breast cancer: is there concordance between standard sections and tissue microarrays?
  Pathology, 38, 316-320.  
17148612 T.S.Wehrman, W.J.Raab, C.L.Casipit, R.Doyonnas, J.H.Pomerantz, and H.M.Blau (2006).
A system for quantifying dynamic protein interactions defines a role for Herceptin in modulating ErbB2 interactions.
  Proc Natl Acad Sci U S A, 103, 19063-19068.  
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.  
15536075 B.Jiang, W.Liu, H.Qu, L.Meng, S.Song, T.Ouyang, and C.Shou (2005).
A novel peptide isolated from a phage display peptide library with trastuzumab can mimic antigen epitope of HER-2.
  J Biol Chem, 280, 4656-4662.
PDB code: 1y2n
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.  
15822127 C.Luo, L.Xu, S.Zheng, X.Luo, J.Shen, H.Jiang, X.Liu, and M.Zhou (2005).
Computational analysis of molecular basis of 1:1 interactions of NRG-1beta wild-type and variants with ErbB3 and ErbB4.
  Proteins, 59, 742-756.  
15688065 C.P.Blobel (2005).
ADAMs: key components in EGFR signalling and development.
  Nat Rev Mol Cell Biol, 6, 32-43.  
15970791 D.G.Cox, S.E.Hankinson, and D.J.Hunter (2005).
The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk.
  Pharmacogenet Genomics, 15, 447-450.  
15812476 G.Bussolati, F.Montemurro, L.Righi, M.Donadio, M.Aglietta, and A.Sapino (2005).
A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer.
  Br J Cancer, 92, 1261-1267.  
16168106 G.von Minckwitz, S.Harder, S.Hövelmann, E.Jäger, S.E.Al-Batran, S.Loibl, A.Atmaca, C.Cimpoiasu, A.Neumann, A.Abera, A.Knuth, M.Kaufmann, D.Jäger, A.B.Maurer, and W.S.Wels (2005).
Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas.
  Breast Cancer Res, 7, R617-R626.  
16153156 J.Chen, H.C.Tseng, M.A.Dichter, H.Zhang, and M.I.Greene (2005).
Differential localization of ErbB receptor ensembles influences their signaling in hippocampal neurons.
  DNA Cell Biol, 24, 553-562.  
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
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.  
15507452 N.K.Dakappagari, K.D.Lute, S.Rawale, J.T.Steele, S.D.Allen, G.Phillips, R.T.Reilly, and P.T.Kaumaya (2005).
Conformational HER-2/neu B-cell epitope peptide vaccine designed to incorporate two native disulfide bonds enhances tumor cell binding and antitumor activities.
  J Biol Chem, 280, 54-63.  
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.  
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
15757908 S.K.Kuwada, J.Kuang, and X.Li (2005).
Integrin alpha5/beta1 expression mediates HER-2 down-regulation in colon cancer cells.
  J Biol Chem, 280, 19027-19035.  
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
15837615 S.R.Hubbard (2005).
EGF receptor inhibition: attacks on multiple fronts.
  Cancer Cell, 7, 287-288.  
15838425 Y.Tang, D.Scollard, P.Chen, J.Wang, C.Holloway, and R.M.Reilly (2005).
Imaging of HER2/neu expression in BT-474 human breast cancer xenografts in athymic mice using [(99m)Tc]-HYNIC-trastuzumab (Herceptin) Fab fragments.
  Nucl Med Commun, 26, 427-432.  
15093533 A.Badache, and N.E.Hynes (2004).
A new therapeutic antibody masks ErbB2 to its partners.
  Cancer Cell, 5, 299-301.  
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.  
15197512 B.M.van der Ende, F.J.Sharom, and J.H.Davis (2004).
The transmembrane domain of Neu in a lipid bilayer: molecular dynamics simulations.
  Eur Biophys J, 33, 596-610.  
  15305184 C.De Lorenzo, A.Tedesco, G.Terrazzano, R.Cozzolino, P.Laccetti, R.Piccoli, and G.D'Alessio (2004).
A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent.
  Br J Cancer, 91, 1200-1204.  
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.  
15235591 J.Kniazeff, A.S.Bessis, D.Maurel, H.Ansanay, L.Prézeau, and J.P.Pin (2004).
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity.
  Nat Struct Mol Biol, 11, 706-713.  
15095281 K.Pulford, S.W.Morris, and F.Turturro (2004).
Anaplastic lymphoma kinase proteins in growth control and cancer.
  J Cell Physiol, 199, 330-358.  
15093539 M.C.Franklin, K.D.Carey, F.F.Vajdos, D.J.Leahy, A.M.de 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
15031492 M.E.Noble, J.A.Endicott, and L.N.Johnson (2004).
Protein kinase inhibitors: insights into drug design from structure.
  Science, 303, 1800-1805.  
15576039 M.Landau, S.J.Fleishman, and N.Ben-Tal (2004).
A putative mechanism for downregulation of the catalytic activity of the EGF receptor via direct contact between its kinase and C-terminal domains.
  Structure, 12, 2265-2275.  
14749123 R.F.Ozols, M.A.Bookman, D.C.Connolly, M.B.Daly, A.K.Godwin, R.J.Schilder, X.Xu, and T.C.Hamilton (2004).
Focus on epithelial ovarian cancer.
  Cancer Cell, 5, 19-24.  
15324690 R.J.Crowder, D.P.Lombardi, and M.J.Ellis (2004).
Successful targeting of ErbB2 receptors-is PTEN the key?
  Cancer Cell, 6, 103-104.  
15196762 S.J.Chiu, N.T.Ueno, and R.J.Lee (2004).
Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine.
  J Control Release, 97, 357-369.  
14744244 T.Holbro, and N.E.Hynes (2004).
ErbB receptors: directing key signaling networks throughout life.
  Annu Rev Pharmacol Toxicol, 44, 195-217.  
15324695 Y.Nagata, K.H.Lan, X.Zhou, M.Tan, F.J.Esteva, A.A.Sahin, K.S.Klos, P.Li, B.P.Monia, N.T.Nguyen, G.N.Hortobagyi, M.C.Hung, and D.Yu (2004).
PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients.
  Cancer Cell, 6, 117-127.  
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.  
12817993 C.J.Witton (2003).
Structure of HER receptors and intracellular localisation of downstream effector elements gives insight into mechanism of tumour growth promotion.
  Breast Cancer Res, 5, 206-207.  
14703062 M.Azemar, S.Djahansouzi, E.Jäger, C.Solbach, M.Schmidt, A.B.Maurer, K.Mross, C.Unger, G.von Minckwitz, P.Dall, B.Groner, and W.S.Wels (2003).
Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2.
  Breast Cancer Res Treat, 82, 155-164.  
12605220 M.X.Sliwkowski (2003).
Ready to partner.
  Nat Struct Biol, 10, 158-159.  
12867596 T.Kumagai, M.Katsumata, A.Hasegawa, K.Furuuchi, T.Funakoshi, I.Kawase, and M.I.Greene (2003).
Role of extracellular subdomains of p185c-neu and the epidermal growth factor receptor in ligand-independent association and transactivation.
  Proc Natl Acad Sci U S A, 100, 9220-9225.  
14639001 Y.Maru (2003).
Tyrosine kinase as molecular target of anti-tumor drug.
  Nippon Yakurigaku Zasshi, 122, 473-481.  
12972807 Y.Yuza, M.Agawa, M.Matsuzaki, H.Yamada, and M.Urashima (2003).
Gene and protein expression profiling during differentiation of neuroblastoma cells triggered by 13-cis retinoic acid.
  J Pediatr Hematol Oncol, 25, 715-720.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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