Ras signalling on the endoplasmic reticulum and the Golgi

VK Chiu, T Bivona, A Hach, JB Sajous, J Silletti… - Nature cell …, 2002 - nature.com
VK Chiu, T Bivona, A Hach, JB Sajous, J Silletti, H Wiener, RL Johnson, AD Cox, MR Philips
Nature cell biology, 2002nature.com
Current models evoke the plasma membrane (PM) as the exclusive platform from which Ras
regulates signalling. We developed a fluorescent probe that reports where and when Ras is
activated in living cells. We show that oncogenic H-Ras and N-Ras engage Raf-1 on the
Golgi and that endogenous Ras and unpalmitoylated H-Ras are activated in response to
mitogens on the Golgi and endoplasmic reticulum (ER), respectively. We also demonstrate
that H-Ras that is restricted to the ER can activate the Erk pathway and transform fibroblasts …
Abstract
Current models evoke the plasma membrane (PM) as the exclusive platform from which Ras regulates signalling. We developed a fluorescent probe that reports where and when Ras is activated in living cells. We show that oncogenic H-Ras and N-Ras engage Raf-1 on the Golgi and that endogenous Ras and unpalmitoylated H-Ras are activated in response to mitogens on the Golgi and endoplasmic reticulum (ER), respectively. We also demonstrate that H-Ras that is restricted to the ER can activate the Erk pathway and transform fibroblasts, and that Ras localized on different membrane compartments differentially engages various signalling pathways. Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane.
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