title: Peroxiredoxin-controlled G-CSF signalling at the endoplasmic reticulum-early endosome interface.
abstract: 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.
authors: Department of Hematology, Erasmus University Medical Center, 3015 GE Rotterdam,  The Netherlands.
authors: Karishma
authors: K
authors: Palande
authors: Onno
authors: O
authors: Roovers
authors: Judith
authors: J
authors: Gits
authors: Carola
authors: C
authors: Verwijmeren
authors: Yoshihito
authors: Y
authors: Iuchi
authors: Junichi
authors: J
authors: Fujii
authors: Benjamin G
authors: BG
authors: Neel
authors: Robert
authors: R
authors: Karisch
authors: Jan
authors: J
authors: Tavernier
authors: Ivo P
authors: IP
authors: Touw
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; C515980:PRDX4 protein, human; D054464:Peroxiredoxins; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1