KEGG   PATHWAY: mjv04380
Entry
mjv04380                    Pathway                                
Name
Osteoclast differentiation - Manis javanica (Malayan pangolin)
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
mjv04380  Osteoclast differentiation
mjv04380

Other DBs
GO: 0030316
Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108383720  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
108383733  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
108384008  IFNG; interferon gamma [KO:K04687]
108384766  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
108384893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108385396  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
108385494  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
108385610  CYBA; cytochrome b-245 light chain isoform X1 [KO:K08009]
108385635  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
108385695  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
108385943  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
108385993  IFNGR2; interferon gamma receptor 2 [KO:K05133]
108386624  [KO:K06512]
108386668  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
108386817  JUN; transcription factor Jun [KO:K04448]
108386879  FOSB; protein FosB isoform X1 [KO:K09029]
108386996  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
108387092  FOSL2; fos-related antigen 2 isoform X1 [KO:K09030]
108387426  [KO:K06463]
108387612  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
108389636  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1 [KO:K06551]
108390300  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108390671  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
108390709  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
108391002  RELB; transcription factor RelB isoform X3 [KO:K09253]
108391263  IRF9; interferon regulatory factor 9 [KO:K04693]
108391436  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
108391706  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
108391749  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
108391859  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
108392654  NCF4; neutrophil cytosol factor 4 [KO:K08012]
108392710  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
108393034  IL1B; interleukin-1 beta [KO:K04519]
108393196  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108393407  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
108393851  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
108394148  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
108394253  NCF2; neutrophil cytosol factor 2 [KO:K08010]
108394347  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
108394635  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
108394636  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108394952  FOSL1; fos-related antigen 1 [KO:K04502]
108395952  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 [KO:K04958]
108395975  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
108396080  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
108396160  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
108396166  NOX1; LOW QUALITY PROTEIN: NADPH oxidase 1 [KO:K08008]
108396443  TMEM64; transmembrane protein 64 [KO:K26770]
108396943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108397005  RELA; transcription factor p65 isoform X1 [KO:K04735]
108397113  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
108397364  [KO:K04403]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108397835  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
108397877  TNF; tumor necrosis factor [KO:K03156]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108399127  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
108399674  JUNB; transcription factor JunB [KO:K09028]
108399795  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108400080  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
108400238  CALCR; calcitonin receptor [KO:K04576]
108400464  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108400537  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
108400653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108400663  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
108400819  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
108400987  CSF1; macrophage colony-stimulating factor 1 [KO:K05453]
108401068  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
108401193  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
108401515  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
108402236  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
108402523  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108402531  IFNB1; interferon beta [KO:K05415]
108402534  FOS; protein c-Fos [KO:K04379]
108402801  FHL2; four and a half LIM domains protein 2 isoform X2 [KO:K14380]
108402938  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X2 [KO:K04960]
108403071  MITF; microphthalmia-associated transcription factor isoform X11 [KO:K09455]
108403151  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
108403293  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
108403805  [KO:K06512]
108403816  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
108404162  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
108404707  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
108405137  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
108405554  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
108405673  NFKB2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
108405993  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
108406004  JUND; transcription factor JunD [KO:K04449]
108406372  BLNK; B-cell linker protein isoform X1 [KO:K07371]
108406827  TRAF2; TNF receptor-associated factor 2 isoform X4 [KO:K03173] [EC:2.3.2.27]
108407315  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
108407415  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
108407595  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
108407802  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
108408263  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
108408573  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
108409505  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
108409586  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108409616  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108410304  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
118966860  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
140843038  [KO:K06512]
140847225  [KO:K06512]
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
mjv04010  MAPK signaling pathway
mjv04020  Calcium signaling pathway
mjv04064  NF-kappa B signaling pathway
mjv04151  PI3K-Akt signaling pathway
mjv04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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