Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
Database (Oxford). 2011 Jul 8;2011:bar021. doi: 10.1093/database/bar021. Print 2011.
Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily that plays a key role in the regulation of differentiation, activation and survival of osteoclasts and also in tumor cell migration and bone metastasis. Osteoclast activation induced by RANKL regulates hematopoietic stem cell mobilization as part of homeostasis and host defense mechanisms thereby linking regulation of hematopoiesis with bone remodeling. Binding of RANKL to its receptor, Receptor activator of nuclear factor-kappa B (RANK) activates molecules such as NF-kappa B, mitogen activated protein kinase (MAPK), nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase (PI3K). Although the molecular and cellular roles of these molecules have been reported previously, a systematic cataloging of the molecular events induced by RANKL/RANK interaction has not been attempted. Here, we present a comprehensive reaction map of the RANKL/RANK-signaling pathway based on an extensive manual curation of the published literature. We hope that the curated RANKL/RANK-signaling pathway model would enable new biomedical discoveries, which can provide novel insights into disease processes and development of novel therapeutic interventions.
核因子-κB 受体激活物配体（RANKL）是肿瘤坏死因子（TNF）超家族的一员，在调节破骨细胞的分化、激活和存活方面发挥着关键作用，同时也在肿瘤细胞迁移和骨转移中发挥作用。RANKL 诱导的破骨细胞激活调节造血干细胞的动员，作为体内平衡和宿主防御机制的一部分，从而将造血调节与骨重塑联系起来。RANKL 与其受体核因子-κB 受体激活物（RANK）结合，激活 NF-κB、丝裂原活化蛋白激酶（MAPK）、活化 T 细胞核因子（NFAT）和磷酸肌醇 3-激酶（PI3K）等分子。尽管先前已经报道了这些分子的分子和细胞作用，但尚未尝试对 RANKL/RANK 相互作用诱导的分子事件进行系统编目。在这里，我们根据已发表文献的广泛人工策展，呈现了 RANKL/RANK 信号通路的综合反应图谱。我们希望经过策展的 RANKL/RANK 信号通路模型能够促进新的生物医学发现，为疾病过程和新型治疗干预措施的发展提供新的见解。
