{"id":106033,"date":"2018-03-11T10:29:48","date_gmt":"2018-03-11T10:29:48","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/regulation-of-the-stability-of-the-protein-kinase-dyrk1aestablishing-connections-with-the-wnt-signaling-pathway\/"},"modified":"2018-03-11T10:29:48","modified_gmt":"2018-03-11T10:29:48","slug":"regulation-of-the-stability-of-the-protein-kinase-dyrk1aestablishing-connections-with-the-wnt-signaling-pathway","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/pompeu-fabra\/regulation-of-the-stability-of-the-protein-kinase-dyrk1aestablishing-connections-with-the-wnt-signaling-pathway\/","title":{"rendered":"Regulation of the stability of the protein kinase dyrk1a:establishing connections with the wnt signaling pathway"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Krisztina Arat\u00f3 <\/strong><\/h2>\n<p>Dyrk1a es el miembro m\u00e1s estudiado de la familia de prote\u00edna quinasas dyrk, porque es una de las prote\u00ednas de el cromosoma humano 21 para la que cambios en la dosis g\u00e9nica dan lugar a alteraciones neuropatol\u00f3gicas. Las quinasas dyrk se activan por autofosforilaci\u00f3n en un residuo tirosina localizado en el lazo de activaci\u00f3n, un evento \u00fanico que ocurre durante la traducci\u00f3n. Como consecuencia, dyrk1a ser\u00eda constitutivamente activa una vez se ha sintetizado. Sin embargo, dyrk1a es extremadamente sensible a la dosis g\u00e9nica, y por tanto es predecible que no s\u00f3lo su actividad, pero tambi\u00e9n los niveles de prote\u00edna han de estar estrictamente controlados por mecanismos reguladores que todav\u00eda no han sido caracterizados. en este trabajo, la prote\u00edna quinasa nlk ha sido identificada como un nuevo regulador de la estabilidad de dyrk1a. Dyrk1a interacciona con nlk en condiciones fisiol\u00f3gicas, y la interacci\u00f3n tiene como resultado la fosforilaci\u00f3n de dyrk1a en residuos serina\/treonina, varios de los cuales han sido identificados por espectrometr\u00eda de masas. La interacci\u00f3n con nlk y la subsecuente fosforilaci\u00f3n promueven la degradaci\u00f3n de dyrk1a v\u00eda el proteasoma. Adem\u00e1s, la degradaci\u00f3n de dyrk1a es inducida por estimulaci\u00f3n de la c\u00e9lulas con wnt1 o wnt3a, o por sobreexpresi\u00f3n de miembros de la cascada de se\u00f1alizaci\u00f3n de wnt, como el receptor frizzled-1 o de un activador de nlk como hipk2. Finalmente, se ha demostrado que dyrk1a se une y fosforila \u00edY-catenina y tcf-4. La fosforilaci\u00f3n de, al menos, \u00edY-catenina es responsable del incremento de la actividad transcripcional dependiente de esta prote\u00edna en presencia de dyrk1a. Todos estos resultados sugieren que dyrk1a act\u00faa como un factor positivo en la v\u00eda de se\u00f1alizaci\u00f3n wnt-\u00edY-catenina y nlk act\u00faa como un regulador negativo al inducir la degradaci\u00f3n v\u00eda proteasoma no s\u00f3lo de los factores de transcripci\u00f3n tcf\/lef sino tambi\u00e9n del modulador positivo dyrk1a.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Regulation of the stability of the protein kinase dyrk1a:establishing connections with the wnt signaling pathway<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Regulation of the stability of the protein kinase dyrk1a:establishing connections with the wnt signaling pathway <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Krisztina Arat\u00f3 <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pompeu fabra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 20\/12\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Susana De La Luna Gargantilla<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: purificacion Mu\u00f1oz canoves <\/li>\n<li>Juan Galcer\u00e1n saez (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Krisztina Arat\u00f3 Dyrk1a es el miembro m\u00e1s estudiado de la familia de prote\u00edna quinasas dyrk, porque es [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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