Akt allows cytosolic regulation of endoplasmic reticulum stress pathways

MATIAS BLAUSTEIN; J ALFARO; D PEREZ; C URRUTIA; M A SANCHEZ; ALICIA GRANDE; GUILLERMO RISSO; B BURKINSHAW; JUAN PABLO FEDEDA; ANABELLA SREBROW; ALEJANDRO COLMAN LERNER

Potrero de Funes

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2011

Society of Biochemistry and Molecular Biology XLVII Reunión Anual Argentina de Investigación en Bioquimica y Biología Molecular

In mammalian cells, Akt protein kinases are recruited to the plasma membrane where they are phosphorylated in response to a wide variety of extracellular signals. Traditionally, Akt regulates a multitude of targets that promote cell survival. On the other hand, the Unfolded Protein Response (UPR) pathways, which typically respond to Endoplasmic Reticulum (ER) signals, have been shown to mantain homeostasis by regulating cell survival and cell death. We studied UPR and Akt activity levels by western blot and RT-PCR and we monitored simultaneously these levels in individual cells by working with specifically designed fluorescent protein-based reporters of IRE1, ATF6, Akt1 and Akt2. Here we propose, by genetic analysis and fluorescence microscopy, that transient modulation of AKT activity allows ER membrane residing Akt molecules to activate UPR. Our results unravel Akt as a novel cytosolic regulator of UPR pathways. This crosstalk emerges as a master control mechanism of cell decision making in terms of survival or death showing the remarkable flexibility of signaling pathways, which can direct cells to opposing fates depending on the dynamics of their activation