Erratum: HER2/Neu: mechanisms of dimerization/oligomerization

Brennan, Patrick J.; Kumagai, Toru; Berezov, Alan; Murali, Ramachandran; Greene, Mark I.

doi:10.1038/sj.onc.1205119

Cited by 18 publications

(10 citation statements)

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“…The ligand-independent activation and self-association of ErbB2 occurs when it is overexpressed at the plasma membrane [ 26 ], and its ECD has been indicated to contribute to this dimerization process [ 14 , 27 ]. Our structure revealed that the ErbB2 ECD plays an essential role in ErbB2 dimerization: two ErbB2 protomers directly bind to each other through an interaction between the dimerization arm and the C-shaped pocket.…”

Section: Discussionmentioning

confidence: 99%

Molecular architecture of the ErbB2 extracellular domain homodimer

Sun

Meng

et al. 2015

Oncotarget

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Human epidermal growth factor receptors (HERs or ErbBs) play crucial roles in numerous cellular processes. ErbB2 is a key member of ErbB family, and its overexpression is recognized as a frequent molecular abnormality. In cancer, this overexpression correlates with aggressive disease and poor patient outcomes. Dimer-dependent phosphorylation is a key event for the signal transduction of ErbBs. However, the molecular mechanism of the dimerization of ErbB2 remains elusive. In the present work, we report the homodimer architecture of the ErbB2 extracellular domain (ECD) which is unique compared with other dimer-models of ErbBs. The structure of the ErbB2 ECD homodimer represents a “back to head” interaction, in which a protruding β-hairpin arm in domain II of one ErbB2 protomer is inserted into a C-shaped pocket created by domains I–III of the adjacent ErbB2 protomer. This dimerized architecture and its impact on the phosphorylation of ErbB2 intracellular domain were further verified by a mutagenesis study. We also elucidated the different impacts of two clinically administered therapeutic antibodies, trastuzumab and pertuzumab, on ErbB2 dimerization. This information not only provides an understanding of the molecular mechanism of ErbBs dimerization but also elucidates ErbB2-targeted therapy at the molecular level.

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Section: Discussionmentioning

confidence: 99%

Molecular architecture of the ErbB2 extracellular domain homodimer

Sun

Meng

et al. 2015

Oncotarget

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“…HER2, being an orphan receptor, does not form homodimers in response to ligands, but forms ligand-independent homodimers in HER2-overexpressing cells ( 4 ). It also associates in heterodimers with other members of the receptor family ( 4 ), thereby contributing significantly to a dysregulation of intracellular signaling ( 5 ) and of cell growth ( 6 ). In principle, the amount of homodimers in a cell population can be quantified, for example with biochemical methods using pooled cellular material.…”

Section: Introductionmentioning

confidence: 99%

Local variations of HER2 dimerization in breast cancer cells discovered by correlative fluorescence and liquid electron microscopy

2015

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“…This has been extremely useful in studying the biochemical and biological responses deriving from the activation of the so-called orphan transmembrane tyrosine kinase receptors, for which no ligand has been identified so far [77,78,79]. …”

Section: Agonist Met Mabsmentioning

confidence: 99%

Monoclonal Antibodies against the MET/HGF Receptor and Its Ligand: Multitask Tools with Applications from Basic Research to Therapy

2014

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Monoclonal antibodies can be seen as valuable tools for many aspects of basic as well as applied sciences. In the case of MET/HGFR, they allowed the identification of truncated isoforms of the receptor, as well as the dissection of different epitopes, establishing structure–function relationships. Antibodies directed against MET extracellular domain were found to be full or partial receptor agonists or antagonists. The agonists can mimic the effects of the different isoforms of the natural ligand, but with the advantage of being more stable than the latter. Thus, some agonist antibodies promote all the biological responses triggered by MET activation, including motility, proliferation, morphogenesis, and protection from apoptosis, while others can induce only a migratory response. On the other hand, antagonists can inhibit MET-driven biological functions either by competing with the ligand or by removing the receptor from the cell surface. Since MET/HGFR is often over-expressed and/or aberrantly activated in tumors, monoclonal antibodies can be used as probes for MET detection or as “bullets” to target MET-expressing tumor cells, thus pointing to their use in diagnosis and therapy.

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Erratum: HER2/Neu: mechanisms of dimerization/oligomerization

Cited by 18 publications

References 0 publications

Molecular architecture of the ErbB2 extracellular domain homodimer

Molecular architecture of the ErbB2 extracellular domain homodimer

Local variations of HER2 dimerization in breast cancer cells discovered by correlative fluorescence and liquid electron microscopy

Monoclonal Antibodies against the MET/HGF Receptor and Its Ligand: Multitask Tools with Applications from Basic Research to Therapy

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