Division of Immunology, Transplantation and Infectious Diseases, DIBIT-San Raffaele Scientific Institute, 20132 Milan, Italy.
Infections and Cancer Biology Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France.
Viruses. 2017 Dec 28;10(1):9. doi: 10.3390/v10010009.
The exposure to CCR5 (CC chemokine receptor 5) specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome. In particular, our data show that β-arrestin2/ERK1 complex is a relevant transducer in the CCR5 signaling pathway. Understanding the mechanism of CCR5 regulation is essential for many inflammatory disorders, tumorigenesis and viral infection such as HIV.
在体外接触 CCR5（CC 趋化因子受体 5）特异性天然抗体，借助 ERK1，形成 CCR5 信号小体，从而产生 B 类β-arrestin2 依赖性 CCR5 保留，该信号小体至少稳定 48 小时。鉴于β-arrestins 和 MAPKs 对环境信号敏感，它们的信号复合物可能是 GPCR 内化相关信号转导的关键连接点之一。在这里，我们证明在 T 细胞中，CCR5 受体或 ERK1 蛋白的磷酸化状态对于将内化的受体驱动到早期内体中形成 CCR5 信号小体是必需的。具体而言，我们的数据表明β-arrestin2/ERK1 复合物是 CCR5 信号通路中的一个相关转导器。了解 CCR5 调节的机制对于许多炎症性疾病、肿瘤发生和病毒感染（如 HIV）至关重要。
