CD254, also known as RANKL, TNFSF11, TRANCE, OPGL and ODF, is a type II membrane protein of the tumor necrosis factor (TNF) superfamily, and affects the immune system and control bone regeneration and remodeling. RANKL is the ligand of nuclear factor (NF)-κB (RANK). When RANKL binds to RANK, it will undergo trimerization and then bind to an adaptor molecule TNF receptor-associated factor 6 (TRAF6). This results in the activation of several downstream signaling cascades, including the NFκB, mitogen-activated protein kinases (MAPK), activating protein 1 (AP-1), and nuclear factor of activated T cells (NFATc1), resulting in the formation of multinucleated bone-resorbing osteoclasts. RANKL is widely expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas.
Receptor Activator of Nuclear Factor κ B (RANK), also known as CD265, TRANCE Receptor or TNFRSF11A, is member of the tumor necrosis factor receptor (TNFR) molecular superfamily. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It plays a vital role in bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. RANK is constitutively expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cell, and pancreas.
Human Chemokine (C-C Motif) Ligand 5 (CCL5) plays an active role in recruiting leukocytes into inflammatory sites. CCL5 is secreted by many cell types at inflammatory sites and it exerts a wide range of activities through the receptors CCR1, CCR3, CCR4, and CCR5. N-Terminal truncated CCL5/RANTES, Met-RANTES, and amino-oxypentane (AOP)-RANTES exhibit antagonist or partial agonist functions on their receptors. CCL5/RANTES attracts different subtypes of leukocytes into inflamed tissue and intervenes in a wide range of allergic and autoimmune diseases.
Retinoic acid receptor responder protein 2(RARRES2) is a secreted protein that in humans is encoded by the RARRES2 gene. It is highly expressed in skin, also found in pancreas, liver, spleen, prostate, ovary, small intestine and colon. It is a chemoattractant protein that acts as a ligand for the G protein-coupled receptor CMKLR1. RARRES2 is secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammatory and coagulation serine proteases. It is thought to act as a cell surface receptor, found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation. RARRES2 is inhibited in psoriatic lesions,it is activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions.
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