RESUMENEl hongo C. albicans forma parte de la microbiota comensal de las mucosas del tracto gastrointestinal y genitourinario de seres humanos. En condiciones de disbiosis o inmunosupresión, se produce una transición de comensal a patógeno en la que se producen cambios morfológicos que tienen relevancia en la producción de daño en las células epiteliales del huésped. La NDR quinasa Cbk1, efector final de la ruta RAM/MOR, desempeña un papel esencial en este proceso de transición morfológica ya que células deficientes en actividad Cbk1 son incapaces de formar hifas. Esta quinasa es capaz de integrar las señales ambientales inductoras del crecimiento hifal aunque se desconocen los mecanismos postraduccionales implicados. Este estudio ha puesto de manifiesto que Cbk1 modifica su patrón de fosforilación en respuesta a suero en dos etapas. Al inicio de la respuesta, durante la formación del tubo germinativo, se produce una rápida desfosforilación que depende de la fosfatasa Cdc14 y de la ruta cAMP-PKA. Posteriormente, durante el mantenimiento del crecimiento hifal, Cbk1 es refosforilada por un mecanismo que depende de la quinasa dependiente de ciclina (Cdk) Cdc28 y de la ciclina específica de miceliación Hgc1. El análisis de los mutantes fosfodeficientes y fosfomiméticos en los posibles residuos fosfoaceptores de Cbk1 han puesto de manifiesto que estas modificaciones son esenciales para mantener el crecimiento polarizado de la hifa e inhibir la separación celular. Además, los resultados derivados de las interacciones génicas con SSD1 nos ha permitido concluir que la función de Cbk1 al inicio de la respuesta a suero consiste en inhibir la función de Ssd1, proteína que reprime la traducción de los mRNAS a los que está unido, mientras que, durante el mantenimiento de la respuesta, su función en el crecimiento hifal es independiente de su control sobre Ssd1. Con el fin de caracterizar mejor el papel de Cbk1 en esta segunda fase, se construyó el mutante cbk1-M412A que dio lugar a una quinasa sensible al análogo 1NM-PP1. El uso de este mutante nos permitió inactivar la quinasa rápidamente cuando las células habían formado hifas. Este tipo de experimentos nos ha permitido concluir que la actividad de Cbk1 es necesaria para mantener a Spa2, componente del polarisoma, localizado en el ápice de la hifa de forma constante e independiente del ciclo celular. También hemos puesto de manifiesto una función no esperada en la parada del ciclo celular de las células subapicales.Por último, en este trabajo hemos profundizado en la regulación de la fosfatasa Cdc14, que también es necesaria para activar el crecimiento hifal en respuesta a suero. Nuestros resultados han permitido identificar a las quinasas Cdc28, Cbk1 y a la propia fosfatasa, como factores importantes que regulan la función de Cdc14. La generación de un mutante catalíticamente inactivo de Cdc14, cdc14-CS, y el estudio de su estado de fosforilación en diferentes fondos genéticos nos ha permitido concluir que Cdc14 se autodesfosforila mediante interacciones intermoleculares, actividad que requiere de la señalización mediada por la ruta RAM/MOR. También, los resultados obtenidos con el mutante condicional cdc28-as sugieren que esta Cdk estabiliza e inhibe la actividad de Cdc14. 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