Destroy and Exploit: Catalyzed Removal of Hydroperoxides from the Endoplasmic Reticulum
Figure 1
RTK signaling involves NOX-derived H2O2 as second messenger. (a) Binding of ligand (L) to receptor tyrosine kinases (RTK) on the cell surface activates NADPH oxidases (NOX) and leads to the generation of extracellular or, following endocytosis, endosomal superoxide (), which can be dismutated to H2O2 (black filled circles). Upon aquaporin 8 (AQP8)-facilitated diffusion across the plasma/endosomal membrane, H2O2 locally inactivates the intracellular negative regulators phosphotyrosine phosphatases (PTPs) and peroxiredoxins (Prxs), which prolongs RTK signal transduction. This step mostly, but not exclusively (as depicted by an asterisk), involves the endoplasmic reticulum (ER)-associated PTP1B. Spatial restriction of H2O2 is achieved by cytosolic ROS scavengers like Prxs. (b) An ER-centered route of RTK-mediated signal transduction involves NOX4 in the ER membrane and PTP1B. In this context, ER-luminal buildup of H2O2 is controlled by ER-resident PrxIV.
