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http://purl.uniprot.org/citations/20026641http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20026641http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20026641http://www.w3.org/2000/01/rdf-schema#comment"Disruption of the gene encoding protein tyrosine kinase 6 (PTK6) leads to increased growth, impaired enterocyte differentiation and higher levels of nuclear beta-catenin in the mouse small intestine. Here, we demonstrate that PTK6 associates with nuclear and cytoplasmic beta-catenin and inhibits beta-catenin- and T-cell factor (TCF)-mediated transcription. PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64. However, mutation of these sites does not abrogate the ability of PTK6 to inhibit beta-catenin transcriptional activity. Outcomes of PTK6-mediated regulation appear to be dependent on its intracellular localization. In the SW620 colorectal adenocarcinoma cell line, nuclear-targeted PTK6 negatively regulates endogenous beta-catenin/TCF transcriptional activity, whereas membrane-targeted PTK6 enhances beta-catenin/TCF regulated transcription. Levels of TCF4 and the transcriptional co-repressor TLE/Groucho increase in SW620 cells expressing nuclear-targeted PTK6. Knockdown of PTK6 in SW620 cells leads to increased beta-catenin/TCF transcriptional activity and increased expression of beta-catenin/TCF target genes Myc and Survivin. Ptk6-null BAT-GAL mice, containing a beta-catenin-activated LacZ reporter transgene, have increased levels of beta-galactosidase expression in the gastrointestinal tract. The ability of PTK6 to negatively regulate beta-catenin/TCF transcription by modulating levels of TCF4 and TLE/Groucho could contribute to its growth-inhibitory activities in vivo."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.org/dc/terms/identifier"doi:10.1242/jcs.053264"xsd:string
http://purl.uniprot.org/citations/20026641http://purl.org/dc/terms/identifier"doi:10.1242/jcs.053264"xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Asara J.M."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Asara J.M."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Zheng Y."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Zheng Y."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Bie W."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Bie W."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Brauer P.M."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Brauer P.M."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Gierut J.J."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Gierut J.J."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Palka-Hamblin H.L."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Palka-Hamblin H.L."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Tyner A.L."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/author"Tyner A.L."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/name"J. Cell Sci."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/name"J. Cell Sci."xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/pages"236-245"xsd:string
http://purl.uniprot.org/citations/20026641http://purl.uniprot.org/core/pages"236-245"xsd:string