Receptor Tyrosine Kinases Activate Canonical WNT/[beta]-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct [beta]-Catenin Phosphorylation
Receptor tyrosine kinase signaling cooperates with WNT/[beta]-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/[beta]-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent o...
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| Veröffentlicht in: | PloS one 2012-04, Vol.7 (4), p.e35826 |
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| creator | 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 |
| description | Receptor tyrosine kinase signaling cooperates with WNT/[beta]-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/[beta]-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 [beta]-catenin at Tyr142, which is known to increase cytoplasmic [beta]-catenin concentration via release of [beta]-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct [beta]-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling. |
| doi_str_mv | 10.1371/journal.pone.0035826 |
| format | Article |
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| subjects | Phenols (Class of compounds) Phosphotransferases Tyrosine |
| title | Receptor Tyrosine Kinases Activate Canonical WNT/[beta]-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct [beta]-Catenin Phosphorylation |
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