Department of Hematology, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands.
J Cell Sci. 2011 Nov 1;124(Pt 21):3695-705. doi: 10.1242/jcs.089656.
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.
活性氧 (ROS) 通过抑制氧化敏感的磷酸酶至少部分调节生长因子受体信号。一个新出现的概念是，ROS 在局部起作用，影响不同亚细胞区室中的信号转导，并且 ROS 水平由同一局部水平的抗氧化蛋白调节。在这里，我们表明内质网驻留的抗氧化剂过氧化物酶 4 (Prdx4) 与粒细胞集落刺激因子受体 (G-CSFR) 的细胞质结构域相互作用。这种相互作用发生在激活的 G-CSFR 位于早期内体时。Prdx4 抑制髓系祖细胞中由 G-CSF 诱导的信号转导和增殖，这取决于其氧化还原活性半胱氨酸核心。蛋白酪氨酸磷酸酶 1b (Ptp1b) 似乎是控制这些反应的主要下游效应物。相反，Ptp1b 可能通过降低其磷酸化来保持 Prdx4 的活性。这些发现揭示了一种新的信号转导调节电路，涉及内质网中氧化还原控制的过程和内体中激活的细胞因子受体。
