RGD Reference Report - Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met-beta-catenin interactions. - Rat Genome Database

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Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met-beta-catenin interactions.

Authors: Zeng, G  Apte, U  Micsenyi, A  Bell, A  Monga, SP 
Citation: Zeng G, etal., Exp Cell Res. 2006 Nov 1;312(18):3620-30. Epub 2006 Aug 10.
RGD ID: 2317517
Pubmed: PMID:16952352   (View Abstract at PubMed)
PMCID: PMC1820835   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yexcr.2006.08.003   (Journal Full-text)

beta-Catenin, a key component of the canonical Wnt pathway, is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor Met at the membrane. HGF induced Met-beta-catenin dissociation and nuclear translocation of beta-catenin, which was tyrosine-phosphorylation-dependent. Here, we further investigate the Met-beta-catenin interaction by selectively mutating several tyrosine residues, alone or in combination, in beta-catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected into rat hepatoma cells, which were treated with HGF. All single or double-mutant-transfected cells continued to show HGF-induced nuclear translocation of FLAG-beta-catenin except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of beta-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of beta-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in beta-catenin are crucial in HGF-mediated beta-catenin translocation, activation and mitogenesis.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
beta-catenin binding  IPICTNNB1 (Homo sapiens)2317517 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Met  (MET proto-oncogene, receptor tyrosine kinase)

Objects referenced in this article
Gene CTNNB1 catenin beta 1 Homo sapiens

Additional Information