%0 Journal Article
%T Receptor Tyrosine Kinases Activate Canonical WNT/¦Â-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct ¦Â-Catenin Phosphorylation
%A Pavel Krejci
%A Anie Aklian
%A Marketa Kaucka
%A Eva Sevcikova
%A Jirina Prochazkova
%A Jan Kukla Masek
%A Pavol Mikolka
%A Tereza Pospisilova
%A Tereza Spoustova
%A MaryAnn Weis
%A William A. Paznekas
%A Joshua H. Wolf
%A J. Silvio Gutkind
%A William R. Wilcox
%A Alois Kozubik
%A Ethylin Wang Jabs
%A Vitezslav Bryja
%A Lisa Salazar
%A Iva Vesela
%A Lukas Balek
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0035826
%X Receptor tyrosine kinase signaling cooperates with WNT/¦Â-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/¦Â-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate ¦Â-catenin at Tyr142, which is known to increase cytoplasmic ¦Â-catenin concentration via release of ¦Â-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct ¦Â-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035826