Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3338780?pdf=render |
| _version_ | 1817968018456576000 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Pavel Krejci |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:03:21Z |
| format | Article |
| id | doaj.art-c0182a0e9b1847789602f32735b60daf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T20:03:21Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c0182a0e9b1847789602f32735b60daf2022-12-22T02:32:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3582610.1371/journal.pone.0035826Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation.Pavel KrejciAnie AklianMarketa KauckaEva SevcikovaJirina ProchazkovaJan Kukla MasekPavol MikolkaTereza PospisilovaTereza SpoustovaMaryAnn WeisWilliam A PaznekasJoshua H WolfJ Silvio GutkindWilliam R WilcoxAlois KozubikEthylin Wang JabsVitezslav BryjaLisa SalazarIva VeselaLukas BalekReceptor 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.http://europepmc.org/articles/PMC3338780?pdf=render |
| spellingShingle | 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 Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. PLoS ONE |
| title | Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. |
| title_full | Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. |
| title_fullStr | Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. |
| title_full_unstemmed | Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. |
| title_short | Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin phosphorylation. |
| title_sort | receptor tyrosine kinases activate canonical wnt β catenin signaling via map kinase lrp6 pathway and direct β catenin phosphorylation |
| url | http://europepmc.org/articles/PMC3338780?pdf=render |
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