KEGG   PATHWAY: setr04380
Entry
setr04380                   Pathway                                
Name
Osteoclast differentiation - Suncus etruscus (white-toothed pygmy shrew)
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
setr04380  Osteoclast differentiation
setr04380

Other DBs
GO: 0030316
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
125995762  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
125996221  TNF; tumor necrosis factor [KO:K03156]
125996324  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125996360  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
125996366  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125997278  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
125997497  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
125997897  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
125998082  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
125998103  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125998575  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
125998702  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
125999080  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
126001180  IRF9; interferon regulatory factor 9 [KO:K04693]
126001285  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126001942  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
126002675  IFNB1; interferon beta [KO:K05415]
126003300  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
126003348  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
126003376  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
126003551  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
126003919  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
126004042  FOS; protein c-Fos [KO:K04379]
126005876  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
126006234  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
126006273  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
126006288  NCF4; neutrophil cytosol factor 4 [KO:K08012]
126006370  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
126006407  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
126006483  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
126006708  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
126006951  TNFRSF1A; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 1A [KO:K03158]
126008206  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
126008959  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
126009005  STAT1; LOW QUALITY PROTEIN: signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
126009097  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
126009254  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
126010825  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
126010979  JUN; transcription factor Jun [KO:K04448]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126011131  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126011869  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
126011898  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126012641  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
126013417  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
126013464  [KO:K12560]
126013658  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
126013977  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
126013988  [KO:K06463]
126014267  NCF2; neutrophil cytosol factor 2 [KO:K08010]
126015660  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
126015663  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
126016258  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
126016597  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
126017341  [KO:K06551]
126017576  [KO:K06551]
126017829  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
126017923  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
126018082  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
126018145  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
126018446  [KO:K06512]
126019025  RELA; transcription factor p65 [KO:K04735]
126019129  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
126020210  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
126020271  ITGB3; integrin beta-3 [KO:K06493]
126020311  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
126020656  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
126021920  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
126022154  STAT2; LOW QUALITY PROTEIN: signal transducer and activator of transcription 2 [KO:K11221]
126022183  IFNG; interferon gamma [KO:K04687]
126022840  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
126023860  FOSL2; LOW QUALITY PROTEIN: fos-related antigen 2 [KO:K09030]
126023992  FHL2; four and a half LIM domains protein 2 [KO:K14380]
126023995  IL1A; interleukin-1 alpha [KO:K04383]
126024019  IL1B; interleukin-1 beta [KO:K04519]
126024218  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
126024674  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
126024780  CALCR; calcitonin receptor [KO:K04576]
126025796  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
126026058  [KO:K05130]
126026073  IFNGR2; interferon gamma receptor 2 [KO:K05133]
126026082  [KO:K05130]
126027082  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
126027269  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
126027532  [KO:K06512]
126027533  [KO:K06512]
126027534  [KO:K06512]
126027544  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
126027678  TYROBP; TYRO protein tyrosine kinase-binding protein [KO:K07992]
126027775  [KO:K08009]
126027877  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
126028133  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126028183  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
126028224  [KO:K04348] [EC:3.1.3.16]
126028249  FOSB; protein FosB [KO:K09029]
126028569  RELB; transcription factor RelB [KO:K09253]
126028681  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
126028683  [KO:K06512]
126028684  [KO:K06512]
126028685  [KO:K06512]
126028686  [KO:K06512]
126028687  [KO:K06512]
126028690  [KO:K06512]
126028691  [KO:K06512]
126028693  [KO:K06512]
126028694  [KO:K06512]
126028695  [KO:K06512]
126028697  [KO:K06512]
126028699  [KO:K06512]
126028700  [KO:K06512]
126028704  [KO:K06512]
126028705  [KO:K06512]
126028706  [KO:K06512]
126028707  [KO:K06512]
126028708  [KO:K06512]
126028712  [KO:K06512]
126028713  [KO:K06512]
126028714  [KO:K06512]
126029440  JUND; transcription factor JunD [KO:K04449]
126029517  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
126029893  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126030254  JUNB; transcription factor JunB [KO:K09028]
126030267  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
126030488  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
126030540  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
126030555  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
126030882  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
126031061  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
126031156  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
126031245  NCF1; neutrophil cytosol factor 1 [KO:K08011]
126031410  IFNGR1; interferon gamma receptor 1 [KO:K05132]
126032054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
126032521  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
126033346  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
126033690  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
126033704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
126033811  NFKB2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
126033816  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
126033854  BLNK; B-cell linker protein [KO:K07371]
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
setr04010  MAPK signaling pathway
setr04020  Calcium signaling pathway
setr04064  NF-kappa B signaling pathway
setr04151  PI3K-Akt signaling pathway
setr04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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