Hsp90 restrains ErbB‐2/HER2 signalling by limiting heterodimer formation
العنوان: | Hsp90 restrains ErbB‐2/HER2 signalling by limiting heterodimer formation |
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المؤلفون: | Ami Citri, Yosef Yarden, Judith Gan, János Szöllosi, Yaron Mosesson, Gyorgi Vereb |
المصدر: | EMBO reports. 5:1165-1170 |
بيانات النشر: | EMBO, 2004. |
سنة النشر: | 2004 |
مصطلحات موضوعية: | animal structures, Receptor, ErbB-2, Amino Acid Motifs, Molecular Sequence Data, Scientific Report, Biology, Biochemistry, Growth factor receptor, ErbB, Genetics, Amino Acid Sequence, HSP90 Heat-Shock Proteins, skin and connective tissue diseases, Receptor, neoplasms, Molecular Biology, Hsp90, Cell biology, Signalling, Protein kinase domain, Cancer research, biology.protein, Signal transduction, Dimerization, Tyrosine kinase, Signal Transduction |
الوصف: | ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers is limited by Hsp90, which is dissociated from ErbB-2 following ligand-induced heterodimerization. We show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby restraining heterodimer formation and catalytic function. These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes. |
تدمد: | 1469-3178 1469-221X |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7072345663f17142072b818398525b1 https://doi.org/10.1038/sj.embor.7400300 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....b7072345663f17142072b818398525b1 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14693178 1469221X |
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