The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors.

By Thomas P. J. Garrett, N. Mckern, M. Lou, T. Elleman, T. Adams, G. Lovrecz, M. Kofler, Robert N. Jorissen, E. Nice, Antony W. Burgess and 1 more. Molecules and Cells, 2003

634 citations recorded by the source corpus.

Subfields: Immunology and Allergy, Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/f9fdea35db158c2016d3a3bac3e0987264352b41

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In Immunology and Allergy

1. N. Hynes
2. R. Roskoski
3. Lewis C. Cantley
4. N. Iqbal
5. T. Yuan
6. N. Iqbal

In Oncology

1. N. Hynes
2. J. Baselga
3. M. Moasser
4. R. Roskoski
5. S. Swain
6. Thomas Holbro
7. M. Wieduwilt
8. D. Leahy

In Radiology, Nuclear Medicine and Imaging

1. N. Hynes
2. J. Baselga
3. M. Moasser
4. R. Roskoski
5. S. Swain
6. Thomas Holbro
7. M. Sliwkowski
8. M. Wieduwilt

Citations in the corpus

• Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. (2006, background): “However, in addition to its function as an individual receptor, EGFR may play an important role as a coreceptor for HER-2 (43).”
• ErbB receptors: directing key signaling networks throughout life. (2004, background): “The structure of ErbB2’s extracellular region revealed a major difference in comparison to ErbB1 and ErbB3 (19, 20).”
• Efficient selection of DARPins with sub-nanomolar affinities using SRP phage display. (2008, background): “e ErbB receptors and in parentheses the amino acids of the mature extracellular domain as described.(47) 1214 Selection of DARPins with Sub-nanomolar Affinities”
• ERBB receptors and cancer: the complexity of targeted inhibitors (2005, background): “ERBB2 has a fixed conformation that resembles the ligand-activated state: the domain II–IV interaction is absent and the dimerization loop in domain II is expose”
• The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis (2007, background): “Unlike the other members of the family, the extracellular domain of HER2 does not pivot between active and inactive conformations and constitutively exists in an activated conformation (Cho et al., 2003; Garrett et al., 2003).”
• The ErbB/HER family of protein-tyrosine kinases and cancer. (2014, background): “The X-ray crystal structure of the extracellular segment of EGFR reveals that the leucine-rich domain I resembles domain III and that the cysteine-rich domain II resembles domain IV [34,36,37].”
• Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (2012, background): “HER2 differs from other family members because it lacks a reported ligand and its extracellular domain is permanently poised in an “active-like” conformation (GrausPorta et al., 1997; Garrett et al., 2003).”
• Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis (2018, background): “constitutively active form makes HER2 the preferred component to form dimers with other molecules and grants HER2 the capability of affecting many cellular functions through various pathways.(108,109) Ligand binding and subsequent dimerization stimulate phosphorylation of tyrosine residues in the in”
• An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. (2003, background): “…explanation for why no ErbB2 ligand lations suggest that both the dimerization arm of sErbB2 and its docking site in domain II are quite negativelyhas ever been identified: the ErbB2 ligand binding site is both obstructed and mutated. charged and may repel one another (Garrett et al., 2003).”
• Mechanism of activation and inhibition of the HER4/ErbB4 kinase. (2008, background): “These unique interactions rationalize the absence of an ErbB2 ligand and the role of ErbB2 as a universal ErbB heterodimerization partner (Cho et al., 2003; Garrett et al., 2003).”
• The epidermal growth factor receptor family: Biology driving targeted therapeutics (2008, background): “Consistent with the inability to identify a ligand for ErbB2, the crystal structure of a truncated ErbB2 ectodomain reveals that the receptor is locked in the extended conformation poised to interact with other receptors [35].”
• Novel anticancer targets: revisiting ERBB2 and discovering ERBB3 (2009, background): “It exists in the extended (open) 'active' conformation state, rendering ERBB2 constitutively available for dimerizatio”