{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:14:55Z","timestamp":1791231295269,"version":"4.1.0"},"reference-count":66,"publisher":"The Company of Biologists","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:p>The Wnt pathways contribute to many processes in cancer and development, with \u03b2-catenin being a key canonical component. p120-catenin, which is structurally similar to \u03b2-catenin, regulates the expression of certain Wnt target genes, relieving repression conferred by the POZ- and zinc-finger-domain-containing transcription factor Kaiso. We have identified the kinase Dyrk1A as a component of the p120-catenin\u2013Kaiso trajectory of the Wnt pathway. Using rescue and other approaches in Xenopus laevis embryos and mammalian cells, we found that Dyrk1A positively and selectively modulates p120-catenin protein levels, thus having an impact on p120-catenin and Kaiso (and canonical Wnt) gene targets such as siamois and wnt11. The Dyrk1A gene resides within the Down's syndrome critical region, which is amplified in Down's syndrome. A consensus Dyrk phosphorylation site in p120-catenin was identified, with a mutant mimicking phosphorylation exhibiting the predicted enhanced capacity to promote endogenous Wnt-11 and Siamois expression, and gastrulation defects. In summary, we report the biochemical and functional relationship of Dyrk1A with the p120-catenin\u2013Kaiso signaling trajectory, with a linkage to canonical Wnt target genes. Conceivably, this work might also prove relevant to understanding the contribution of Dyrk1A dosage imbalance in Down's syndrome.<\/jats:p>","DOI":"10.1242\/jcs.086173","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T16:11:08Z","timestamp":1330963868000},"page":"561-569","source":"Crossref","is-referenced-by-count":46,"title":["Down's-syndrome-related kinase Dyrk1A modulates the p120-catenin\u2013Kaiso trajectory of the Wnt signaling pathway"],"prefix":"10.1242","volume":"125","author":[{"given":"Ji Yeon","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"},{"name":"Program in Genes and Development, University of Texas Graduate School of Biomedical Science, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Il","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, Tx 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moonsup","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"},{"name":"Program in Genes and Development, University of Texas Graduate School of Biomedical Science, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"},{"name":"Program in Genes and Development, University of Texas Graduate School of Biomedical Science, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel K.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"},{"name":"Program in Genes and Development, University of Texas Graduate School of Biomedical Science, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Ezan","sequence":"additional","affiliation":[{"name":"Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei Y.","family":"Sokol","sequence":"additional","affiliation":[{"name":"Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre D.","family":"McCrea","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA"},{"name":"Program in Genes and Development, University of Texas Graduate School of Biomedical Science, Houston, Texas, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042522062420600_R1","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1093\/hmg\/10.18.1915","article-title":"Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome","volume":"10","author":"Altafaj","year":"2001","journal-title":"Hum. 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