RGD Reference Report - The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity. - Rat Genome Database

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The evolutionarily conserved EBR module of RALT/MIG6 mediates suppression of the EGFR catalytic activity.

Authors: Anastasi, S  Baietti, MF  Frosi, Y  Alema, S  Segatto, O 
Citation: Anastasi S, etal., Oncogene. 2007 Dec 13;26(57):7833-46. Epub 2007 Jun 18.
RGD ID: 8553726
Pubmed: PMID:17599051   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1210590   (Journal Full-text)

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 activity in vitro and in intact cells. The mechanism involves binding of the EBR to the 953RYLVIQ958 sequence, which is located in the alphaI 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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Errfi1Ratnegative regulation of epidermal growth factor-activated receptor activity involved_inIDA PMID:17599051UniProt 
Errfi1Ratnegative regulation of peptidyl-tyrosine phosphorylation involved_inIDA PMID:17599051UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Errfi1Ratkinase binding enablesIPIUniProtKB:P00533PMID:17599051UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Errfi1  (ERBB receptor feedback inhibitor 1)


Additional Information