{"id":62888,"date":"2018-03-09T22:50:47","date_gmt":"2018-03-09T22:50:47","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/analisis-molecular-del-transporte-nucleocitoplasmatico-de-ksr1\/"},"modified":"2018-03-09T22:50:47","modified_gmt":"2018-03-09T22:50:47","slug":"analisis-molecular-del-transporte-nucleocitoplasmatico-de-ksr1","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ciencias-de-la-vida\/analisis-molecular-del-transporte-nucleocitoplasmatico-de-ksr1\/","title":{"rendered":"An\u00e1lisis molecular del transporte nucleocitoplasm\u00e1tico de ksr1."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Luis Gustavo P\u00e9rez Rivas <\/strong><\/h2>\n<p>Ksr1 (kinase suppressor of ras 1) es una prote\u00edna scaffold de la ruta ras\/raf\/mek\/erk. Ksr1 se localiza mayoritariamente en el citosol y se traslada a la membrana plasm\u00e1tica tras la activaci\u00f3n de erk1\/2. Para este proceso es necesaria una de las cinco regiones conservadas de ksr1, el dominio ca3. En la presente memoria hemos identificado una secuencia de localizaci\u00f3n nuclear en ksr1, a la que hemos denominado k-nls, correspondiente a los residuos 383-plarlrrte-391. Esta secuencia, similar a la nls de c-myc, result\u00f3 ser la responsable del transporte de ksr1 al n\u00facleo, pues la sustituci\u00f3n de los residuos r386 y r389 por metioninas evit\u00f3 la acumulaci\u00f3n de ksr1 en el n\u00facleo en experimentos de bloqueo de la exportaci\u00f3n y caus\u00f3 la redistribuci\u00f3n de un mutante nuclear (ksr1-mut) en el citosol. Adem\u00e1s, hemos observado una interacci\u00f3n entre ksr1 y componentes del sistema de transporte, en concreto las importinas \u00c2\u00bf5, \u00c2\u00bf7 y \u00edY, y que el dominio ca3 era necesario. La adici\u00f3n de importinas \u00c2\u00bf5 y \u00c2\u00bf7 favoreci\u00f3 la acumulaci\u00f3n in vitro de una fusi\u00f3n bsa-k-nls en el n\u00facleo de c\u00e9lulas hela permeabilizadas con digitonina, mientras que la mutaci\u00f3n de la secuencia k-nls redujo la interacci\u00f3n entre ksr1 e importinas \u00c2\u00bf in vivo. Finalmente, hemos determinado una correlaci\u00f3n, entre  la localizaci\u00f3n nuclear de ksr1 y el estado de activaci\u00f3n de erk1\/2 tanto in vitro como in vivo. Tanto la estimulaci\u00f3n con egf y la sobreexpresi\u00f3n de erk1 silvestre redistribuyeron a ksr1-mut en el citosol, pero, sin embargo, un mutante de erk1\/2 quinasa inactivo fue incapaz de producir este efecto. Asimismo, mutaciones que mimetizaron la fosforilaci\u00f3n de ksr1 por erk1\/2 redujeron la asociaci\u00f3n entre ksr1 e importina \u00edY. Muy notablemente, hemos detectado que ksr1 end\u00f3geno puede distribuirse tanto en el citosol como en el n\u00facleo, aunque la localizaci\u00f3n de ksr1 en tejidos tumorales, caracterizados por una activaci\u00f3n constitutiva de erk1\/2, es exclusivamente citoplasm\u00e1tica en conclusi\u00f3n, los resultados mostrados en la presente memoria permiten establecer un nuevo modelo de regulaci\u00f3n de ksr1 en el cual la fosforilaci\u00f3n por erk1\/2 evita el transporte de ksr1 al n\u00facleo, aumentando su concentraci\u00f3n local en la membrana y favoreciendo una mayor activaci\u00f3n de ekr1\/2.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>An\u00e1lisis molecular del transporte nucleocitoplasm\u00e1tico de ksr1.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 An\u00e1lisis molecular del transporte nucleocitoplasm\u00e1tico de ksr1. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Luis Gustavo P\u00e9rez Rivas <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 M\u00e1laga<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 13\/02\/2008<\/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>Jos\u00e9 Lozano Castro<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: federico Mayor menendez <\/li>\n<li>pedro Lazp-zbikowski taracema (vocal)<\/li>\n<li>francisca Mar\u00eda Sanchez jimenez (vocal)<\/li>\n<li>miren edurne Berra ram\u00edrez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Luis Gustavo P\u00e9rez Rivas Ksr1 (kinase suppressor of ras 1) es una prote\u00edna scaffold de la ruta [&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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