The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity
| Autor: | Stefano Alemà, Oreste Segatto, Maria Francesca Baietti, Y Frosi, Sergio Anastasi |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Biology Catalysis Conserved sequence Evolution Molecular Mice ErbB Receptors Growth factor receptor Ubiquitin Genetics Animals Humans Phosphorylation Binding site Molecular Biology Cells Cultured Conserved Sequence Adaptor Proteins Signal Transducing Feedback Physiological Binding Sites Tumor Suppressor Proteins Molecular biology Protein Structure Tertiary Cell biology biology.protein Signal transduction Tyrosine kinase Signal Transduction |
| Zdroj: | Oncogene (Basingstoke) 26 (2007): 7833–7846. info:cnr-pdr/source/autori:Anastasi S., Baietti M.F., Frosi Y., Alemà S. and Segatto O./titolo:The evolutionarily conserved EBR module of RALT%2FMIG6 mediates suppression of the EGFR catalytic activity/doi:/rivista:Oncogene (Basingstoke)/anno:2007/pagina_da:7833/pagina_a:7846/intervallo_pagine:7833–7846/volume:26 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210590 |
| Popis: | Physiological signalling by the epidermal growth factor receptor (EGFR) controls developmental processes and tissue homeostasis, whereas aberrant EGFR activity drives oncogenic cell transformation. Under normal conditions, the EGFR must therefore generate outputs of defined strength and duration. To this aim, cells balance EGFR activity via different modalities of negative signalling. Increasing attention is being drawn on transcriptionally controlled feedback inhibitors of EGFR, namely RALT/MIG6, LRIG1, SOCS4 and SOCS5. Genetic studies in mice have revealed the essential role of Ralt/Mig6 in regulating Egfr-driven skin morphogenesis and tumour formation, yet the mechanisms through which RALT abrogates EGFR activity are still undefined. We report that RALT suppresses EGFR function by inhibiting its catalytic activity. The evolutionarily conserved ErbB-binding region (EBR) is necessary and sufficient to carry out RALT-dependent suppression of EGFR kinase activityin vitro and in intact cells. The mechanism involves binding of the EBR to the 953RYLVIQ958 sequence, which is located in thealphaI helix of the EGFR kinase and has been shown to participate in allosteric control of EGFR catalytic activity. Our results uncover a novel mechanism of temporal regulation of EGFR activity in vertebrate organisms.Oncogene advance online publication, 18 June 2007; doi:10.1038/sj.onc.1210590. |
| Databáze: | OpenAIRE |
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