protein_function: Cytokine that binds to TNFRSF11B,OPG and toTNFRSF11A,RANK. Osteoclast differentiation and activation factor.Augments the ability of dendritic cells to stimulate naive T-cellproliferation. May be an important regulator of interactionsbetween T-cells and dendritic cells and may play a role in theregulation of the T-cell-dependent immune response. May also playan important role in enhanced bone-resorption in humoralhypercalcemia of malignancy. Induces osteoclastogenesis byactivating multiple signaling pathways in osteoclast precursorcells, chief among which is induction of long lasting oscillationsin the intracellular concentration of Ca (2+) resulting in theactivation of NFATC1, which translocates to the nucleus andinduces osteoclast-specific gene transcription to allowdifferentiation of osteoclasts. During osteoclast differentiation,in a TMEM64 and ATP2A2-dependent manner induces activation ofCREB1 and mitochondrial ROS generation necessary for properosteoclast generation..
Receptor activator of nuclear factor kappa-B ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), is a protein that in humans is encoded by the TNFSF11 gene. This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. The rat gene is mapped to 15q11. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. This gene may play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
