Vaccine and Immunotherapy Center, Boston, MA, USA.
Department of Medicine, Imperial College School of Medicine, London, England.
FASEB J. 2021 Apr;35(4):e21260. doi: 10.1096/fj.202001273R.
Historically the chemokine receptor CXCR4 and its canonical ligand CXCL12 are associated with the bone marrow niche and hematopoiesis. However, CXCL12 exhibits broad tissue expression including brain, thymus, heart, lung, liver, kidney, spleen, and bone marrow. CXCR4 can be considered as a node which is integrating and transducing inputs from a range of ligand-receptor interactions into a responsive and divergent network of intracellular signaling pathways that impact multiple cellular processes such as proliferation, migration, and stress resistance. Dysregulation of the CXCR4/CXCL12 axis and consequent fundamental cellular processes, are associated with a panoply of disease. This review frames the polyfunctionality of the receptor at a molecular, physiological, and pathophysiological levels. Transitioning our perspective of this axis from a single gene/protein:single function model to a polyfunctional signaling cascade highlights the potential for finer therapeutic intervention and cautions against a reductionist approach.
从历史上看，趋化因子受体 CXCR4 及其经典配体 CXCL12 与骨髓龛和造血有关。然而，CXCL12 表现出广泛的组织表达，包括脑、胸腺、心脏、肺、肝、肾、脾和骨髓。CXCR4 可以被视为一个节点，它将来自一系列配体-受体相互作用的输入整合并转导为一个响应性和多样化的细胞内信号通路网络，从而影响多种细胞过程，如增殖、迁移和应激抵抗。CXCR4/CXCL12 轴的失调以及随之而来的基本细胞过程与多种疾病有关。这篇综述从分子、生理和病理生理水平上构建了受体的多功能性。将我们对该轴的观点从单个基因/蛋白：单一功能模型转变为多功能信号级联，突出了更精细的治疗干预的潜力，并告诫人们不要采用还原论方法。
