학술논문
Receptor Tyrosine Kinases Activate Canonical WNT/β-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct β-Catenin Phosphorylation.
Document Type
Article
Author
Krejci, Pavel; Aklian, Anie; Kaucka, Marketa; Sevcikova, Eva; Prochazkova, Jirina; Masek, Jan Kukla; Mikolka, Pavol; Pospisilova, Tereza; Spoustova, Tereza; Weis, MaryAnn; Paznekas, William A.; Wolf, Joshua H.; Gutkind, J. Silvio; Wilcox, William R.; Kozubik, Alois; Jabs, Ethylin Wang; Bryja, Vitezslav; Salazar, Lisa; Vesela, Iva; Balek, Lukas
Source
Subject
*PROTEIN-tyrosine kinases
*CATENINS
*PHOSPHORYLATION
*CYTOPLASM
*CELL adhesion molecules
*CYTOSKELETAL proteins
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Language
ISSN
1932-6203
Abstract
Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-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 b-catenin at Tyr142, which is known to increase cytoplasmic β-catenin concentration via release of β-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct β-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling. [ABSTRACT FROM AUTHOR]