{"id":3860,"date":"2020-01-13T13:52:45","date_gmt":"2020-01-13T13:52:45","guid":{"rendered":"http:\/\/www.sci.muni.cz\/ofiz\/?p=3860"},"modified":"2020-05-12T08:59:30","modified_gmt":"2020-05-12T08:59:30","slug":"comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs","status":"publish","type":"post","link":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/","title":{"rendered":"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs."},"content":{"rendered":"\n<figure class=\"wp-block-image\"><img loading=\"lazy\" decoding=\"async\" width=\"665\" height=\"388\" src=\"https:\/\/www.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/publikace_phosphomap.jpg\" alt=\"\" class=\"wp-image-3861\" srcset=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/publikace_phosphomap.jpg 665w, https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/publikace_phosphomap-300x175.jpg 300w\" sizes=\"auto, (max-width: 665px) 100vw, 665px\" \/><\/figure>\n\n\n\n<p style=\"text-align: right;\"><a href=\"https:\/\/biosignaling.biomedcentral.com\/\" data-test=\"journal-link\"><i data-test=\"journal-title\">Cell Communication and Signaling<\/i><\/a> <b data-test=\"journal-volume\"><span class=\"u-visually-hidden\">volume<\/span>&nbsp;17<\/b>, Article&nbsp;number:&nbsp;<span data-test=\"article-number\">170<\/span> (<span data-test=\"article-publication-year\">2019<\/span>)<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">BACKGROUND:<\/h4>\n\n\n\n<p>Dishevelled (DVL) is an essential component of the Wnt signaling \ncascades. The function of DVL is controlled by phosphorylation but the \nmolecular details are missing. DVL3 contains 131 serines and threonines \nwhose phosphorylation generates complex barcodes underlying diverse DVL3\n functions. In order to dissect the role of DVL phosphorylation we \nanalyzed the phosphorylation of human DVL3 induced by previously \nreported (CK1\u03b5, NEK2, PLK1, CK2\u03b1, RIPK4, PKC\u03b4) and newly identified \n(TTBK2, Aurora A) DVL kinases.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">METHODS:<\/h4>\n\n\n\n<p>Shotgun proteomics including TiO<sub>2<\/sub> enrichment of \nphosphorylated peptides followed by liquid chromatography-tandem mass \nspectrometry on immunoprecipitates from HEK293T cells was used to \nidentify and quantify phosphorylation of DVL3 protein induced by 8 \nkinases. Functional characterization was performed by in-cell analysis \nof phospho-mimicking\/non-phosphorylatable DVL3 mutants and supported by \nFRET assays and NMR spectroscopy.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">RESULTS:<\/h4>\n\n\n\n<p>We used quantitative mass spectrometry and calculated site \noccupancies and quantified phosphorylation of &gt;\u200980 residues. \nFunctional validation demonstrated the importance of CK1\u03b5-induced \nphosphorylation of S268 and S311 for Wnt-3a-induced \u03b2-catenin \nactivation. S630-643 cluster phosphorylation by CK1, NEK2 or TTBK2 is \nessential for even subcellular distribution of DVL3 when induced by CK1 \nand TTBK2 but not by NEK2. Further investigation showed that NEK2 \nutilizes a different mechanism to promote even localization of DVL3. \nNEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents \nbinding of DVL C-terminus to PDZ and promotes an open conformation of \nDVL3 that is more prone to even subcellular localization.<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">CONCLUSIONS:<\/h4>\n\n\n\n<p>We identify unique phosphorylation barcodes associated with DVL \nfunction. Our data provide an example of functional synergy between \nphosphorylation in structured domains and unstructured IDRs that \ntogether dictate the biological outcome.<\/p>\n\n\n\n<p style=\"text-align:right\"><strong>Read the whole story <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/31870452\">HERE<\/a>. \ufeff<\/strong><\/p>\n\n\n\n<p>Han\u00e1kov\u00e1 K, <strong>Bernat\u00edk O<\/strong>, <strong>Kravec M<\/strong>, <strong>Micka M<\/strong>, Kumar J, <strong>Harno\u0161 J<\/strong>, Ovesn\u00e1 P, <strong>Pacl\u00edkov\u00e1 P<\/strong>, <strong>R\u00e1dsetoulal M<\/strong>, Pot\u011b\u0161il D, Tripsianes K, \u010caj\u00e1nek L, Zdr\u00e1hal Z, <strong>Bryja V<\/strong>. <\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cell Communication and Signaling volume&nbsp;17, Article&nbsp;number:&nbsp;170 (2019) BACKGROUND: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. The function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose &hellip; <a href=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\">Read More<\/a><\/p>\n","protected":false},"author":5,"featured_media":3862,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"kt_blocks_editor_width":"","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[412,252],"tags":[304],"class_list":["post-3860","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-bryjalab","category-nova-publikace","tag-bryjalab"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.1.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. - Department of Animal Physiology and Immunology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. - Department of Animal Physiology and Immunology\" \/>\n<meta property=\"og:description\" content=\"Cell Communication and Signaling volume&nbsp;17, Article&nbsp;number:&nbsp;170 (2019) BACKGROUND: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. The function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose &hellip; Read More\" \/>\n<meta property=\"og:url\" content=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Animal Physiology and Immunology\" \/>\n<meta property=\"article:published_time\" content=\"2020-01-13T13:52:45+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-05-12T08:59:30+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/phosphomap.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1224\" \/>\n\t<meta property=\"og:image:height\" content=\"584\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Lucie Nesvadbov\u00e1\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Lucie Nesvadbov\u00e1\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\"},\"author\":{\"name\":\"Lucie Nesvadbov\u00e1\",\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/#\/schema\/person\/3119766c8e4c78f08bbbde220469aee6\"},\"headline\":\"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs.\",\"datePublished\":\"2020-01-13T13:52:45+00:00\",\"dateModified\":\"2020-05-12T08:59:30+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\"},\"wordCount\":328,\"publisher\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/#organization\"},\"image\":{\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/phosphomap.jpg\",\"keywords\":[\"Bryjalab\"],\"articleSection\":[\"Bryjalab\",\"Nov\u00e1 publikace\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\",\"url\":\"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/\",\"name\":\"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. - 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Department of Animal Physiology and Immunology","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/","og_locale":"en_US","og_type":"article","og_title":"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. - Department of Animal Physiology and Immunology","og_description":"Cell Communication and Signaling volume&nbsp;17, Article&nbsp;number:&nbsp;170 (2019) BACKGROUND: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. The function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose &hellip; Read More","og_url":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/","og_site_name":"Department of Animal Physiology and Immunology","article_published_time":"2020-01-13T13:52:45+00:00","article_modified_time":"2020-05-12T08:59:30+00:00","og_image":[{"width":1224,"height":584,"url":"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/phosphomap.jpg","type":"image\/jpeg"}],"author":"Lucie Nesvadbov\u00e1","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Lucie Nesvadbov\u00e1","Est. reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/#article","isPartOf":{"@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/"},"author":{"name":"Lucie Nesvadbov\u00e1","@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/#\/schema\/person\/3119766c8e4c78f08bbbde220469aee6"},"headline":"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs.","datePublished":"2020-01-13T13:52:45+00:00","dateModified":"2020-05-12T08:59:30+00:00","mainEntityOfPage":{"@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/"},"wordCount":328,"publisher":{"@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/#organization"},"image":{"@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/#primaryimage"},"thumbnailUrl":"https:\/\/ueb1.sci.muni.cz\/ofiz\/wp-content\/uploads\/2020\/01\/phosphomap.jpg","keywords":["Bryjalab"],"articleSection":["Bryjalab","Nov\u00e1 publikace"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/","url":"https:\/\/ueb1.sci.muni.cz\/ofiz\/comparative-phosphorylation-map-of-dishevelled-3-links-phospho-signatures-to-biological-outputs\/","name":"Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs. - 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