RANK Signaling in Osteoclasts
Receptor activator of NF-κB ligand (RANKL), also known as OPGL, TRANCE, ODF and TNFSF11, is a member of the TNF family. RANKL and its receptor, RANK (TNFRSF11A) are key regulators of bone remodeling and are essential for the development and activation of osteoclasts. RANKL induces the differentiation of osteoclast precursor cells and stimulates the resorption and survival of mature osteoclasts. Bone remodeling results from the coordinate action of bone resorption by osteoclasts and the formation of new bone by osteoblasts. TRAF adaptor proteins play an important role in initial events of the signal transduction pathways induced by RANK...
Pathway Summary
Receptor activator of NF-κB ligand (RANKL), also known as OPGL, TRANCE, ODF and TNFSF11, is a member of the TNF family. RANKL and its receptor, RANK (TNFRSF11A) are key regulators of bone remodeling and are essential for the development and activation of osteoclasts. RANKL induces the differentiation of osteoclast precursor cells and stimulates the resorption and survival of mature osteoclasts. Bone remodeling results from the coordinate action of bone resorption by osteoclasts and the formation of new bone by osteoblasts. TRAF adaptor proteins play an important role in initial events of the signal transduction pathways induced by RANK. TRAF2, TRAF5 and TRAF6 bind through a conserved domain to RANK. Among the TRAF proteins, TRAF6 is especially critical for RANK signaling in osteoclasts. TRAF proteins act by activating downstream, Raf/MEK/ERK, MEKK/MKK7/JNK and IKK/NF-κB signaling pathways. These pathways activate various transcriptions factors such as Elk-1, MITF and NFAT2 which increase the expression of osteogenic genes, leading to osteoclast differentiation.TRAF6 plays an important role in osteoclast survival and resorption. Src and the TAB2-TAK1 complex are mediators of TRAF6 signaling. Among the many molecules downstream of Src, PYK2 and c-Cbl are implicated in osteoclast adhesion signaling and bone resorption function. While the association of the actin-binding protein gelsolin with PI3K is important in actin filament formation in osteoclasts, Src activates the PI3K/AKT pathway for osteoclast survival.Increased osteoclast activity is seen in many osteopenic disorders including postmenopausal osteoporosis, Paget's disease, lytic bone metastases and rheumatoid arthritis, leading to increased bone resorption and crippling bone damage. Inhibition of RANKL function via the natural decoy receptor OPG prevents bone loss in postmenopausal osteoporosis and cancer metastases, and is useful to treat osteoporosis and bone loss and pain associated with bone metastases.
RANK Signaling in Osteoclasts Genes list
Explore Genes related to RANK Signaling in Osteoclasts
AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 BIRC2baculoviral IAP repeat containing 2 BIRC3baculoviral IAP repeat containing 3 CALML5calmodulin like 5 CBLCbl proto-oncogene CHP1calcineurin like EF-hand protein 1 CHUKcomponent of inhibitor of nuclear factor kappa B kinase complex ELK1ETS transcription factor ELK1 ELP1elongator acetyltransferase complex subunit 1 FOSFos proto-oncogene, AP-1 transcription factor subunit GSNgelsolin IKBKBinhibitor of nuclear factor kappa B kinase subunit beta IKBKEinhibitor of nuclear factor kappa B kinase subunit epsilon IKBKGinhibitor of nuclear factor kappa B kinase regulatory subunit gamma JUNJun proto-oncogene, AP-1 transcription factor subunit MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP2K4mitogen-activated protein kinase kinase 4 MAP2K6mitogen-activated protein kinase kinase 6 MAP2K7mitogen-activated protein kinase kinase 7 MAP3K1mitogen-activated protein kinase kinase kinase 1 MAP3K10mitogen-activated protein kinase kinase kinase 10 MAP3K11mitogen-activated protein kinase kinase kinase 11 MAP3K12mitogen-activated protein kinase kinase kinase 12 MAP3K13mitogen-activated protein kinase kinase kinase 13 MAP3K14mitogen-activated protein kinase kinase kinase 14 MAP3K15mitogen-activated protein kinase kinase kinase 15 MAP3K2mitogen-activated protein kinase kinase kinase 2 MAP3K3mitogen-activated protein kinase kinase kinase 3 MAP3K4mitogen-activated protein kinase kinase kinase 4 MAP3K5mitogen-activated protein kinase kinase kinase 5 MAP3K6mitogen-activated protein kinase kinase kinase 6 MAP3K7mitogen-activated protein kinase kinase kinase 7 MAP3K8mitogen-activated protein kinase kinase kinase 8 MAP3K9mitogen-activated protein kinase kinase kinase 9 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MITFmelanocyte inducing transcription factor NFATC1nuclear factor of activated T cells 1 NFATC2nuclear factor of activated T cells 2 NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NFKBIANFKB inhibitor alpha NFKBIBNFKB inhibitor beta NFKBIDNFKB inhibitor delta NFKBIENFKB inhibitor epsilon PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PPP3CAprotein phosphatase 3 catalytic subunit alpha PPP3CBprotein phosphatase 3 catalytic subunit beta PPP3CCprotein phosphatase 3 catalytic subunit gamma PPP3R1protein phosphatase 3 regulatory subunit B, alpha PPP3R2protein phosphatase 3 regulatory subunit B, beta PTK2Bprotein tyrosine kinase 2 beta RAF1Raf-1 proto-oncogene, serine/threonine kinase RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit SRCSRC proto-oncogene, non-receptor tyrosine kinase TAB2TGF-beta activated kinase 1 (MAP3K7) binding protein 2 TNFRSF11ATNF receptor superfamily member 11a TNFSF11TNF superfamily member 11 TRAF2TNF receptor associated factor 2 TRAF5TNF receptor associated factor 5 TRAF6TNF receptor associated factor 6 XIAPX-linked inhibitor of apoptosis
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