IndraLab
Statements
"Bcr-abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylationthe notion that y86 and y654 are located respectively within the n_ and c_terminal transcriptional domains of __catenin suggests that one or both residues might regulate the transactivating function of __catenin. In this regard, phosphorylation of y654 was reported to strengthen __catenin association with the basal transcription factor tata_binding protein (tbp)"
"Because SHP-1 can dephosphorylate residues Y86 and Y654 on the β-catenin protein, these residues were therefore mutated into phenylalanine and the transcriptional activity of the subsequent β-catenin mutants analyzed: β-catenin/Y86F, β-catenin/Y654F and β-catenin/Y86F/Y654F. As shown in Fig. 3 B, the mutants β-catenin/Y86F, β-catenin/Y654F and β-catenin/Y86F/Y654F had a significantly reduced transcriptional activity in comparison to wild-type β-catenin.|SHP-1 inhibits β-catenin function by inducing its degradation and interfering with its association with TATA-binding protein."
"Beta-catenin is a good substrate of pp60c- src tyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654,although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation."
"One possible explanation is that activation of β-catenin by EGFR mutants may “prime” pulmonary cells to be susceptible to other downstream signaling aberrations and subsequent transformation into tumor cells.|beta-catenin is phosphorylated at Y86 by Src and oncogenic Bcr-Abl and at Y654 by activated wild type EGFR and oncogenic FLT3-ITD."