Peroxiredoxin-controlled G-CSF signalling at the endoplasmic reticulum-early endosome interface

Karishma Palande, Onno Roovers, JHC Gits, Carola Verwijmeren, Y Iuchi, J Fujii, BG Neel, R Karisch, J Tavernier, Ivo Touw

Research output: Contribution to journalArticleAcademicpeer-review

44 Citations (Scopus)


Reactive oxygen species (ROS) regulate growth factor receptor signalling at least in part by inhibiting oxidation-sensitive phosphatases. An emerging concept is that ROS act locally to affect signal transduction in different subcellular compartments and that ROS levels are regulated by antioxidant proteins at the same local level. Here, we show that the ER-resident antioxidant peroxiredoxin 4 (Prdx4) interacts with the cytoplasmic domain of the granulocyte colony-stimulating factor receptor (G-CSFR). This interaction occurs when the activated G-CSFR resides in early endosomes. Prdx4 inhibits G-CSF-induced signalling and proliferation in myeloid progenitors, depending on its redox-active cysteine core. Protein tyrosine phosphatase 1b (Ptp1b) appears to be a major downstream effector controlling these responses. Conversely, Ptp1b might keep Prdx4 active by reducing its phosphorylation. These findings unveil a new signal transduction regulatory circuitry involving redox-controlled processes in the ER and activated cytokine receptors in endosomes.
Original languageUndefined/Unknown
Pages (from-to)3695-3705
Number of pages11
JournalJournal of Cell Science
Issue number21
Publication statusPublished - 2011

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