KEGG   PATHWAY: lcat04380
Entry
lcat04380                   Pathway                                
Name
Osteoclast differentiation - Lemur catta (Ring-tailed lemur)
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
lcat04380  Osteoclast differentiation
lcat04380

Other DBs
GO: 0030316
Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123620460  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
123620572  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
123620633  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
123621038  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
123621580  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
123621731  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
123621799  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123621805  SQSTM1; sequestosome-1 [KO:K14381]
123622180  SIRPB1; signal-regulatory protein beta-1 isoform X1 [KO:K06551]
123622514  [KO:K06551]
123622732  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
123623010  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
123623574  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123623954  FOSB; protein fosB [KO:K09029]
123623971  RELB; transcription factor RelB isoform X1 [KO:K09253]
123624079  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
123624189  [KO:K06512]
123624322  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123624448  [KO:K07992]
123624664  [KO:K06512]
123624667  [KO:K06512]
123624675  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
123624677  [KO:K06512]
123624684  [KO:K06512]
123624818  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
123625377  [KO:K08009]
123625473  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
123625491  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
123626067  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
123626228  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123626515  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123626609  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
123626839  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123627031  NCF2; neutrophil cytosol factor 2 [KO:K08010]
123627206  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123627290  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123627295  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123627566  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123627989  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
123628501  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
123629856  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123630278  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123630694  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
123630696  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
123630699  IFNGR2; interferon gamma receptor 2 [KO:K05133]
123631548  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
123631625  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
123631724  TNF; tumor necrosis factor [KO:K03156]
123632381  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
123632523  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
123632639  NCF1; neutrophil cytosol factor 1 [KO:K08011]
123632778  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
123632820  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
123632869  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123632871  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123632901  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
123633076  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
123633175  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
123633306  IFNGR1; interferon gamma receptor 1 [KO:K05132]
123633357  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
123633892  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
123633926  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
123634187  [KO:K02649]
123634210  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
123634506  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123634842  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
123635010  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
123635228  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A isoform X1 [KO:K06463]
123635230  [KO:K12560]
123635482  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
123635562  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
123635592  JUN; transcription factor AP-1 [KO:K04448]
123635834  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
123636470  IL1A; interleukin-1 alpha [KO:K04383]
123636751  FOSL2; fos-related antigen 2 [KO:K09030]
123636996  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
123637166  IL1B; interleukin-1 beta [KO:K04519]
123637232  JUNB; transcription factor jun-B [KO:K09028]
123637267  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
123637288  FHL2; four and a half LIM domains protein 2 isoform X1 [KO:K14380]
123637973  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
123638075  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
123638104  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
123638832  JUND; transcription factor jun-D [KO:K04449]
123639303  NCF4; neutrophil cytosol factor 4 isoform X1 [KO:K08012]
123639648  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
123639706  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123639915  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
123640135  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
123640344  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
123640661  IFNG; interferon gamma [KO:K04687]
123640770  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123640771  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
123641318  FOSL1; fos-related antigen 1 [KO:K04502]
123641353  RELA; transcription factor p65 isoform X1 [KO:K04735]
123642288  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
123642600  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
123642675  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
123643619  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
123643797  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123644073  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123644708  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B isoform X1 [KO:K05148]
123644774  TMEM64; transmembrane protein 64 isoform X1 [KO:K26770]
123645603  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
123645740  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
123645745  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
123646249  IFNB1; interferon beta [KO:K05415]
123646461  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
123646534  FOS; proto-oncogene c-Fos [KO:K04379]
123647144  CALCR; calcitonin receptor [KO:K04576]
123648496  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
123648578  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123648860  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
123649775  BLNK; B-cell linker protein isoform X1 [KO:K07371]
123650084  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
123650127  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123650134  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
123650296  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
123650465  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123650624  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
123650792  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123650803  IRF9; interferon regulatory factor 9 [KO:K04693]
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
lcat04010  MAPK signaling pathway
lcat04020  Calcium signaling pathway
lcat04064  NF-kappa B signaling pathway
lcat04151  PI3K-Akt signaling pathway
lcat04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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