KEGG   PATHWAY: oor04380
Entry
oor04380                    Pathway                                
Name
Osteoclast differentiation - Orcinus orca (killer whale)
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
oor04380  Osteoclast differentiation
oor04380

Other DBs
GO: 0030316
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101269212  MAPK13; mitogen-activated protein kinase 13 isoform X7 [KO:K04441] [EC:2.7.11.24]
101269458  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101269768  CALCR; calcitonin receptor isoform X1 [KO:K04576]
101269793  RELB; transcription factor RelB [KO:K09253]
101269870  TNF; tumor necrosis factor [KO:K03156]
101269992  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
101270000  [KO:K06463]
101270027  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
101270119  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
101270188  CTSK; cathepsin K isoform X3 [KO:K01371] [EC:3.4.22.38]
101270342  RELA; transcription factor p65 isoform X1 [KO:K04735]
101270586  [KO:K06512]
101271019  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
101271318  [KO:K06512]
101271418  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
101271441  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101272095  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101272154  [KO:K08530]
101272232  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
101272428  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101272432  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
101272458  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
101272616  IL1A; interleukin-1 alpha isoform X1 [KO:K04383]
101272815  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
101272877  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101273049  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
101273237  SPI1; transcription factor PU.1 isoform X2 [KO:K09438]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101273316  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101273696  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
101273825  TMEM64; transmembrane protein 64 [KO:K26770]
101274018  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X3 [KO:K04392]
101274029  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
101274393  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
101274948  [KO:K08009]
101275028  FHL2; four and a half LIM domains protein 2 isoform X2 [KO:K14380]
101275188  ITGB3; integrin beta-3 [KO:K06493]
101275332  TEC; tyrosine-protein kinase Tec isoform X5 [KO:K07364] [EC:2.7.10.2]
101275383  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101276054  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101276254  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101276678  NCF1; neutrophil cytosol factor 1 isoform X2 [KO:K08011]
101277553  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
101277568  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101277609  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
101277656  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
101277657  [KO:K06512]
101277899  [KO:K06512]
101278062  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
101278075  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101278152  TREM2; triggering receptor expressed on myeloid cells 2 isoform X2 [KO:K14378]
101278346  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
101278517  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X3 [KO:K04348] [EC:3.1.3.16]
101278934  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
101278974  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101279266  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
101279441  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101279857  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101280047  FOSL2; fos-related antigen 2 isoform X4 [KO:K09030]
101280083  JUND; transcription factor JunD [KO:K04449]
101280413  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101280894  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101281072  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101281155  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101281228  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
101281303  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101281352  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101281591  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
101281971  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
101281998  JUNB; transcription factor JunB [KO:K09028]
101282502  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101282522  BTK; tyrosine-protein kinase BTK isoform X2 [KO:K07370] [EC:2.7.10.2]
101282675  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X2 [KO:K04403]
101282737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101282933  IFNG; interferon gamma [KO:K04687]
101283011  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101283030  [KO:K12560]
101283250  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
101283533  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
101283653  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
101283958  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
101283961  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101284215  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101284310  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
101284365  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101284420  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
101284466  NOX1; LOW QUALITY PROTEIN: NADPH oxidase 1 [KO:K08008]
101284835  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
101284843  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101284892  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
101284929  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101285095  SIRPB1; signal-regulatory protein beta-1 isoform X1 [KO:K06551]
101285216  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101285437  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101285576  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
101285763  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101286197  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
101286366  FOSB; protein FosB isoform X1 [KO:K09029]
101286388  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101286416  SQSTM1; sequestosome-1 [KO:K14381]
101286650  FOS; protein c-Fos [KO:K04379]
101286693  BLNK; B-cell linker protein isoform X2 [KO:K07371]
101286888  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
101286938  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
101287555  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
101287579  [KO:K04441] [EC:2.7.11.24]
101287685  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
101287701  MAPK9; mitogen-activated protein kinase 9 isoform X5 [KO:K04440] [EC:2.7.11.24]
101287833  [KO:K04441] [EC:2.7.11.24]
101288079  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431] [EC:2.7.12.2]
101288103  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101288913  JUN; transcription factor Jun [KO:K04448]
101289018  NCF4; neutrophil cytosol factor 4 [KO:K08012]
101289058  IFNB1; interferon beta [KO:K05415]
101289351  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101289477  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101289479  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101289855  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101289976  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
105748080  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
125964005  [KO:K06463]
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
oor04010  MAPK signaling pathway
oor04020  Calcium signaling pathway
oor04064  NF-kappa B signaling pathway
oor04151  PI3K-Akt signaling pathway
oor04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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