Open AccessOncogenic Mutants of RON and MET Receptor Tyrosine Kinases Cause Activation of the β-Catenin Pathway
Author(s) -
Alla DanilkovitchMiagkova,
Alexei Miagkov,
Alison Skeel,
Noboru Nakaigawa,
Berton Zbar,
Edward J. Leonard
Publication year - 2001
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.21.17.5857-5868.2001
Subject(s) - biology , adenomatous polyposis coli , wnt signaling pathway , receptor tyrosine kinase , catenin , beta catenin , cancer research , cyclin d1 , tyrosine kinase , tyrosine phosphorylation , signal transduction , carcinogenesis , kinase , microbiology and biotechnology , cell , gene , cell cycle , cancer , genetics , colorectal cancer
beta-Catenin is an oncogenic protein involved in regulation of cell-cell adhesion and gene expression. Accumulation of cellular beta-catenin occurs in many types of human cancers. Four mechanisms are known to cause increases in beta-catenin: mutations of beta-catenin, adenomatous polyposis coli, or axin genes and activation of Wnt signaling. We report a new cause of beta-catenin accumulation involving oncogenic mutants of RON and MET receptor tyrosine kinases (RTKs). Cells transfected with oncogenic RON or MET were characterized by beta-catenin tyrosine phosphorylation and accumulation; constitutive activation of a Tcf transcriptional factor; and increased levels of beta-catenin/Tcf target oncogene proteins c-myc and cyclin D1. Interference with the beta-catenin pathway reduced the transforming potential of mutated RON and MET. Activation of beta-catenin by oncogenic RON and MET constitutes a new pathway, which might lead to cell transformation by these and other mutant growth factor RTKs.