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146 results on '"Kozubik, Alois"'

5. Receptor Tyrosine Kinases Activate Canonical WNT/?-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct Beta-Catenin Phosphorylation

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, and Balek, Lukas

Subjects
wnt, insulin, fgfr3, lrp6, mutations, dysplasia, mechanism, cancer
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 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.

Published
2012

7. Analysis of STAT1 Activation by Six FGFR3 Mutants Associated with Skeletal Dysplasia Undermines Dominant Role of STAT1 in FGFR3 Signaling in Cartilage

Author

Krejci, Pavel, Salazar, Lisa, Kashiwada, Tamara A., Chlebova, Katarina, Salasova, Alena, Thompson, Leslie Michels, Bryja, Vitezslav, Kozubik, Alois, and Wilcox, William R.

Abstract

Activating mutations in FGFR3 tyrosine kinase cause several forms of human skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not completely understood, it is believed that the STAT1 transcription factor plays a central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3 caused activatory STAT1(Y701) phosphorylation. Similarly, in RCS chondrocytes, HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong STAT1 activation. Other FGFR3 mutants caused weak (HeLa) or no activation (293T and RCS). This contrasted with ERK MAP kinase activation, which was strongly induced by all six mutants and correlated with the inhibition of proliferation in RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the K650M and K650E-FGFR3 mutants, which however account for only a small minority of the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should therefore be considered as central to pathological FGFR3 signaling in cartilage.

Published
2008

9. Supplementary Table 1 from Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia

Author

Janovska, Pavlina, primary, Poppova, Lucie, primary, Plevova, Karla, primary, Plesingerova, Hana, primary, Behal, Martin, primary, Kaucka, Marketa, primary, Ovesna, Petra, primary, Hlozkova, Michaela, primary, Borsky, Marek, primary, Stehlikova, Olga, primary, Brychtova, Yvona, primary, Doubek, Michael, primary, Machalova, Michaela, primary, Baskar, Sivasubramanian, primary, Kozubik, Alois, primary, Pospisilova, Sarka, primary, Pavlova, Sarka, primary, and Bryja, Vitezslav, primary

Published
2023
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10. Fibroblast growth factor and canonical WNT/β-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage

Author

Buchtova, Marcela, Oralova, Veronika, Aklian, Anie, Masek, Jan, Vesela, Iva, Ouyang, Zhufeng, Obadalova, Tereza, Konecna, Zaneta, Spoustova, Tereza, Pospisilova, Tereza, Matula, Petr, Varecha, Miroslav, Balek, Lukas, Gudernova, Iva, Jelinkova, Iva, Duran, Ivan, Cervenkova, Iveta, Murakami, Shunichi, Kozubik, Alois, Dvorak, Petr, Bryja, Vitezslav, and Krejci, Pavel

Published
2015
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