RasGRF Couples Nox4-Dependent Endoplasmic Reticulum Signaling to Ras.

ABSTRACT:

Objectives

In response to endoplasmic reticulum (ER) stress, endothelial cells initiate corrective pathways such as the unfolded protein response. Recent studies suggest that reactive oxygen species produced on the ER may participate in homeostatic signaling through Ras in response to ER stress. We sought to identify mechanisms responsible for this focal signaling pathway.

Approach and results

In endothelial cells, we found that ER stress induced by tunicamycin activates the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 focally on the ER surface but not on the plasma membrane. Ras activation is also restricted to the ER, occurs downstream of Nox4, and is required for activation of the unfolded protein response. In contrast, treatment with the growth factor

SUBMITTER: Wu RF 

PROVIDER: S-EPMC5222703 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature