| Autor: |
Pavel Krejci, Anie Aklian, Marketa Kaucka, Eva Sevcikova, Jirina Prochazkova, Jan Kukla Masek, Pavol Mikolka, Tereza Pospisilova, Tereza Spoustova, MaryAnn Weis, William A Paznekas, Joshua H Wolf, J Silvio Gutkind, William R Wilcox, Alois Kozubik, Ethylin Wang Jabs, Vitezslav Bryja, Lisa Salazar, Iva Vesela, Lukas Balek |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 7, Iss 4, p e35826 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0035826 |
| Popis: |
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 β-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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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