RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway (Homo sapiens)

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RELB19, 27, 43, 65, 83704512, 13DissociationCalcineurinCa2+RANKL/RANK Signaling PathwayOsteoclastogenesisSYKFHL2MAP2K6NFKB1LYNRAC1MAP2K1MITFPGTP17, 35, 5429, 67PTNFRSF11BMAP2K7TRAF6Ub14, 30, 50TNFSF11GAB2P2, 23TNFRSF11ATRAF2TRAF3TRAF5TRAF1PIK3R1NFATC1PIK3R2STAT149, 79PIKBKGIKBKBAKT1P17, 22, 43, 58NFKBIA11, 20, 26, 58PMAPK911, 14, 58PMAP3K7PLCG11, 10, 67PJUN2, 3, 58, 72, 76PPTK2P17, 32RELA11, 85PAKT2PMAPK8P2, 14, 31, 37, 42...MAPK314, 17, 39, 57, 58PMAPK114, 17, 39, 57PMAPK1411, 23, 74PCHUKP30, 43, 65MTORP5, 71SRCP1, 17, 60TNFSF11TNFSF1118, 77TNFRSF11ATNFRSF11A61, 642, 823, 51, 803, 52, 803, 52, 803, 51, 8035, 44, 6331, 37TAB2TAB154, 635, 1339, 48, 543954, 636, 31, 3775, 84IP324, 36, 47, 67, 72NFATC121, 24, 26RELA36MAPK14CYCYNUCBLP7, 4838, 54NU3615, 70CYNU1, 232335, 74ROS45, 8134, 66CDC42GTPCALCRNFATC1ACP5SQSTM1FOS14, 25NFKB1TNFRSF11A6846828ICAM1VCAM1CTSK556833, 59SPI19, 41, 62MAP3K1416, 78NFKB246P56, 69NFKB226CYNURELB40, 4836, 53


Receptor activator of nuclear factor-kappa B ligand (RANKL) is a member of tumor necrosis factor (TNF) superfamily. It binds to Receptor activator of NF-kB (RANK) and plays a major role in the regulation of osteoclast function. Binding of RANKL to RANK leads to the activation of signaling modules such as NF-kappa B, mitogen activated protein kinases (MAPK's), protein kinase C (PKC), Ca2+/Calcineurin/nuclear factor of activated T cells (NFAT) and phosphatidyl 3-kinase (PI3K). The RANKL-RANK signaling system is negatively regulated by a decoy receptor known as Osteoprotegerin.

Source: NethPath and NetSlim

Additional comments: RANKL signaling pathway is available at NetPath (http://www.netpath.org). The NetSlim map of the pathway is available at http://www.netpath.org/netslim. This is a collaborative effort between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and Institute of Bioinformatics (http://www.ibioinformatics.org). This pathway is published in Database [PMID:21742767]. If you use this pathway, you must cite following paper: Raju, R., Balakrishnan, L., Nanjappa, V., Bhattacharjee, M., Getnet, D., Muthusamy, B., Thomas, J. K., Sharma, J., Rahiman, B. A., Harsha, H. C., Shankar, S., Prasad, T. S. K., Mohan, S. S., Bader, G. D., Wani, M. R. and Pandey, A. (2011). A comprehensive manually curated reaction map of RANKL/RANK signaling pathway. Database.

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115690view13:10, 4 March 2021DeSlUpdated description, without adding special characters.
115689view13:07, 4 March 2021DeSlReverted to version '12:07, 16 August 2019' by DeSl
115686view19:32, 3 March 2021AlexanderPicoModified description
106175view12:07, 16 August 2019MaintBotHMDB identifier normalization
90016view19:25, 8 October 2016AlexanderPicoModified description
87426view11:50, 22 July 2016MkutmonModified description
86033view12:21, 28 June 2016EveloModified title
86032view12:20, 28 June 2016EveloModified title
79959view13:10, 28 April 2015Zariannotated IP3 metabolite
79274view21:28, 19 March 2015Zari
78555view10:31, 7 January 2015MaintBotadded missing graphIds
74133view06:04, 1 April 2014EgonwFixed the typing of ROS: the ID is found in the Metabolites mapping file.
74079view14:36, 27 March 2014EgonwGave ROS an ID.
71702view19:53, 17 October 2013MaintBotremoved data source from nodes without identifier
70099view18:45, 12 July 2013MaintBotupdated to 2013 schema
67621view11:34, 26 June 2013DdiglesOntology Term : 'signaling pathway pertinent to development' added !
48442view14:50, 24 May 2012NetPathModified description
45591view09:58, 18 October 2011JyotiModified description
45590view09:57, 18 October 2011JyotiModified description
44630view18:15, 22 September 2011Khanspersupdating content
44130view04:52, 25 August 2011JyotiOntology Term : 'signaling pathway' added !
44080view18:16, 23 August 2011MaintBotAdded category and cleaned up MAPP Info
43947view10:31, 19 August 2011JyotiModified description
43946view10:23, 19 August 2011JyotiNew pathway

External references


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NameTypeDatabase referenceComment
ACP5Protein54 (Entrez Gene)
AKT1Protein207 (Entrez Gene) AKT1 undergoes induced phosphorylation upon stimulation with RANKL at Thr-308 and Ser-473 in mouse bone marrow derived macrophages and in maouse macrophage cell line, RAW264.7.
AKT2Protein208 (Entrez Gene)
CALCRProtein799 (Entrez Gene)
CBLProtein867 (Entrez Gene) RANKL stimulation induced the phosphorylation of CBL at Tyr-731 in mouse macrophage-like cell line, RAW264.7
CDC42Protein998 (Entrez Gene)
CHUKProtein1147 (Entrez Gene) CHUK undergoes induced phosphorylation upon stimulation with RANKL in human umbilical vein endothelial cells (HUVECs) and RAW264.7 cells
CTSKProtein1513 (Entrez Gene) Type your comment here
FHL2GeneProduct2274 (Entrez Gene)
FOSProtein2353 (Entrez Gene)
GAB2Protein9846 (Entrez Gene)
ICAM1Protein3383 (Entrez Gene)
IKBKBProtein3551 (Entrez Gene)
IKBKGProtein8517 (Entrez Gene)
JUNProtein3725 (Entrez Gene) JUN undergoes induced phosphorylatin at Ser-63 and Ser-73 in mouse bone marrow derived macrophages, preosteoclasts and 293 cells. Amino acid residues 340-421 of TNFRSF11A are required for its activation
LYNGeneProduct4067 (Entrez Gene)
MAP2K1GeneProduct5604 (Entrez Gene) RANKL stimulation induces MEK1 phosphorylation in RAW264.7 cells
MAP2K6GeneProduct5608 (Entrez Gene)
MAP2K7Protein5609 (Entrez Gene)
MAP3K14Protein9060 (Entrez Gene) RANKL stimulation leads to the activation of alternative NF-kappa B pathway which induced the formation of p52/RELB heterodimers through the activation of MAP3K14 (NIK). NIK deficient mice impairs RANKL mediated osteoclastogenesis.
MAP3K7Protein6885 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
  • MAPK1 undergoes induced phosphorylation upon RANKL stimulation in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and in dendritic cells.
  • Type your comment here
MAPK3Protein5595 (Entrez Gene) MAPK3 undergoes induced phosphorylation upon stimulation with RANKL at Thr-202 and Tyr-204 in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and dendritic cells.
MAPK8Protein5599 (Entrez Gene) RANKL induces MAPK8 phosphorylation at Ser 183 and Tyr-185 in mouse bone marrow macrophages and preosteoclasts
MAPK9Protein5601 (Entrez Gene) RANKL induces MAPK9 phosphorylation at Thr-183 and Tyr-185 in mouse bone marrow derived macrophages.
MITFGeneProduct4286 (Entrez Gene)
MTORProtein2475 (Entrez Gene) MTOR undergoes autophosphorylation upon stimulation with RANKL in osteoclasts and RAW264.7 murine macrophage cells.
NFATC1Protein4772 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NFKB2GeneProduct4791 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene) NFKBIA undergoes induced phosphorylation at Ser-32 in mouse bone marrow macrophages and in RAW264.7 cells.
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PLCG1Protein5335 (Entrez Gene) RANKL stimulation induces PLCG1 phosphorylation in bone marrow derived macrophages and RAW264.7 cells.
PTK2Protein5747 (Entrez Gene) RANKL stimulation induces PTK2 phosphorylation in human umbilical vein endothelial (HUVEC) cells and RAW264.7 cells
RAC1Protein5879 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RELBProtein5971 (Entrez Gene)
SPI1GeneProduct6688 (Entrez Gene)
SQSTM1GeneProduct8878 (Entrez Gene) TRAF6 undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages.
SRCProtein6714 (Entrez Gene) SRC undergoes induced phosphorylation at tyrosine residue upon stimulation with RANKL in murine bone marrow derived macrophages, pre-osteoclasts and in RAW264.7 cells.
STAT1Protein6772 (Entrez Gene) RANKL stimulation induces STAT1 phosphorylation at Ser-727 in mouse pre-osteoclasts and bone marrow macrophages
SYKGeneProduct6850 (Entrez Gene) RANKL stimulation induces SYK phosphorylation at Tyr-323 and Tyr-352 in mouse derived bone marrow cells and RAW264.7 cells
TAB1Protein10454 (Entrez Gene)
TAB2Protein23118 (Entrez Gene)
TNFRSF11AProtein8792 (Entrez Gene)
TNFRSF11BProtein4982 (Entrez Gene)
TNFSF11Protein8600 (Entrez Gene) RANKL self associates to form a homotrimer.
TRAF1Protein7185 (Entrez Gene)
TRAF2Protein7186 (Entrez Gene)
TRAF3Protein7187 (Entrez Gene)
TRAF5Protein7188 (Entrez Gene)
TRAF6GeneProduct7189 (Entrez Gene) TRAF6 undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages.
VCAM1Protein7412 (Entrez Gene)

Annotated Interactions

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