KEGG   PATHWAY: rfq04380
Entry
rfq04380                    Pathway                                
Name
Osteoclast differentiation - Rhinolophus ferrumequinum (greater horseshoe bat)
Description
The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast.
Class
Organismal Systems; Development and regeneration
Pathway map
rfq04380  Osteoclast differentiation
rfq04380

Other DBs
GO: 0030316
Organism
Rhinolophus ferrumequinum (greater horseshoe bat) [GN:rfq]
Gene
117014994  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
117016537  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
117013296  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
117017296  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117027443  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117035064  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
117037029  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
117027160  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
117024531  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117038261  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
117018458  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117035083  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117023560  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117029185  IFNG; interferon gamma [KO:K04687]
117020615  IFNGR1; interferon gamma receptor 1 [KO:K05132]
117036042  IFNGR2; interferon gamma receptor 2 [KO:K05133]
117025725  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
117019304  IL1A; interleukin-1 alpha [KO:K04383]
117019267  IL1B; interleukin-1 beta [KO:K04519]
117033297  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
117020338  TNF; tumor necrosis factor [KO:K03156]
117028184  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
117035087  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
117018527  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
117032431  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
117015163  TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
117036921  TGFBR2; LOW QUALITY PROTEIN: TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
117021430  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
117038716  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
117033796  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
117031652  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
117030261  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
117027840  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
117020052  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
117013869  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
117036177  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
117035380  RELB; transcription factor RelB [KO:K09253]
117035904  NFKB2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
117020162  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
117029047  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X1 [KO:K04403]
117020204  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
117020791  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
117021384  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
117024116  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
117030742  RELA; transcription factor p65 isoform X1 [KO:K04735]
117022439  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
117016044  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
117011750  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
117032413  IFNB1; interferon beta [KO:K05415]
117022968  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117013904  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
117020595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
117029085  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
117029232  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
117016461  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
117037761  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
117026302  mitogen-activated protein kinase 8-like [KO:K04440] [EC:2.7.11.24]
117035933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117022220  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
117016634  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
117024158  FOS; proto-oncogene c-Fos [KO:K04379]
117035643  FOSB; protein fosB isoform X1 [KO:K09029]
117032843  FOSL2; fos-related antigen 2 isoform X1 [KO:K09030]
117030050  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
117027175  JUN; transcription factor AP-1 [KO:K04448]
117037717  JUND; transcription factor jun-D [KO:K04449]
117038370  JUNB; transcription factor jun-B [KO:K09028]
117016447  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
117025704  NOX1; NADPH oxidase 1 isoform X1 [KO:K08008]
117035466  cytochrome b-245 light chain [KO:K08009]
117015215  NCF2; neutrophil cytosol factor 2 [KO:K08010]
117025330  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
117028328  NCF4; neutrophil cytosol factor 4 [KO:K08012]
117024681  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
117021993  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
117034511  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
117034503  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
117034506  leukocyte immunoglobulin-like receptor subfamily A member 5 isoform X1 [KO:K06512]
117034508  leukocyte immunoglobulin-like receptor subfamily A member 5 isoform X1 [KO:K06512]
117034712  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
117035428  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
117034859  leukocyte immunoglobulin-like receptor subfamily B member 4 [KO:K06512]
117034882  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
117015259  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
117014583  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b [KO:K12560]
117014648  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A [KO:K06463]
117020341  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
117015735  tyrosine-protein phosphatase non-receptor type substrate 1-like isoform X1 [KO:K06551]
117015977  signal-regulatory protein beta-1-like [KO:K06551]
117016181  signal-regulatory protein beta-1-like [KO:K06551]
117034989  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
117031968  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
117035915  BLNK; B-cell linker protein [KO:K07371]
117016883  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
117034806  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
117037173  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
117028439  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
117020871  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
117017773  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
117019508  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
117013297  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
117034176  TMEM64; transmembrane protein 64 [KO:K26770]
117035970  PPP3CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
117022051  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117037738  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117032505  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
117033213  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
117024996  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
117025697  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117029996  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
117036993  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
117014590  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
117037388  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
117012130  CALCR; calcitonin receptor [KO:K04576]
117013435  ITGB3; integrin beta-3 [KO:K06493]
117037017  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
117035219  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
117036856  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
117026596  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
117038141  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
117028885  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
117022771  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
117019816  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
117014077  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
117030648  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
117020125  FHL2; four and a half LIM domains protein 2 isoform X1 [KO:K14380]
117034734  CYLD; LOW QUALITY PROTEIN: ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
117016671  SQSTM1; sequestosome-1 [KO:K14381]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:18722561
  Authors
Caetano-Lopes J, Canhao H, Fonseca JE
  Title
Osteoimmunology--the hidden immune regulation of bone.
  Journal
Autoimmun Rev 8:250-5 (2009)
DOI:10.1016/j.autrev.2008.07.038
Reference
PMID:18451259
  Authors
Lorenzo J, Horowitz M, Choi Y
  Title
Osteoimmunology: interactions of the bone and immune system.
  Journal
Endocr Rev 29:403-40 (2008)
DOI:10.1210/er.2007-0038
Reference
PMID:17869613
  Authors
David JP
  Title
Osteoimmunology: a view from the bone.
  Journal
Adv Immunol 95:149-65 (2007)
DOI:10.1016/S0065-2776(07)95005-1
Reference
PMID:16313342
  Authors
Jimi E, Ghosh S
  Title
Role of nuclear factor-kappaB in the immune system and bone.
  Journal
Immunol Rev 208:80-7 (2005)
DOI:10.1111/j.0105-2896.2005.00329.x
Reference
PMID:12748652
  Authors
Boyle WJ, Simonet WS, Lacey DL
  Title
Osteoclast differentiation and activation.
  Journal
Nature 423:337-42 (2003)
DOI:10.1038/nature01658
Reference
PMID:17633024
  Authors
Darnay BG, Besse A, Poblenz AT, Lamothe B, Jacoby JJ
  Title
TRAFs in RANK signaling.
  Journal
Adv Exp Med Biol 597:152-9 (2007)
DOI:10.1007/978-0-387-70630-6_12
Reference
PMID:15122243
  Authors
Baron R
  Title
Arming the osteoclast.
  Journal
Nat Med 10:458-60 (2004)
DOI:10.1038/nm0504-458
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20703218
  Authors
Krum SA, Chang J, Miranda-Carboni G, Wang CY
  Title
Novel functions for NFkappaB: inhibition of bone formation.
  Journal
Nat Rev Rheumatol 6:607-11 (2010)
DOI:10.1038/nrrheum.2010.133
Reference
PMID:15817678
  Authors
Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY
  Title
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation.
  Journal
Blood 106:852-9 (2005)
DOI:10.1182/blood-2004-09-3662
Reference
PMID:18329366
  Authors
Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H
  Title
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals.
  Journal
Cell 132:794-806 (2008)
DOI:10.1016/j.cell.2007.12.037
Reference
PMID:15546140
  Authors
Takayanagi H, Kim S, Koga T, Taniguchi T
  Title
Stat1-mediated cytoplasmic attenuation in osteoimmunology.
  Journal
J Cell Biochem 94:232-40 (2005)
DOI:10.1002/jcb.20316
Reference
PMID:18382763
  Authors
Jin W, Chang M, Paul EM, Babu G, Lee AJ, Reiley W, Wright A, Zhang M, You J, Sun SC
  Title
Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice.
  Journal
J Clin Invest 118:1858-66 (2008)
DOI:10.1172/JCI34257
Reference
PMID:16184196
  Authors
Bai S, Kitaura H, Zhao H, Chen J, Muller JM, Schule R, Darnay B, Novack DV, Ross FP, Teitelbaum SL
  Title
FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner.
  Journal
J Clin Invest 115:2742-51 (2005)
DOI:10.1172/JCI24921
Reference
PMID:12110142
  Authors
Takayanagi H, Kim S, Taniguchi T
  Title
Signaling crosstalk between RANKL and interferons in osteoclast differentiation.
  Journal
Arthritis Res 4 Suppl 3:S227-32 (2002)
DOI:10.1186/ar581
Related
pathway
rfq04010  MAPK signaling pathway
rfq04020  Calcium signaling pathway
rfq04064  NF-kappa B signaling pathway
rfq04151  PI3K-Akt signaling pathway
rfq04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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