KEGG   PATHWAY: mlf04380
Entry
mlf04380                    Pathway                                
Name
Osteoclast differentiation - Myotis lucifugus (little brown 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
mlf04380  Osteoclast differentiation
mlf04380

Other DBs
GO: 0030316
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102417174  [KO:K06512]
102417209  IFNB1; interferon beta [KO:K05415]
102417312  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4 [KO:K07209] [EC:2.7.11.10]
102417337  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
102417355  JUNB; transcription factor jun-B [KO:K09028]
102417411  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
102417432  FHL2; four and a half LIM domains protein 2 [KO:K14380]
102417433  FOS; proto-oncogene c-Fos [KO:K04379]
102417484  [KO:K06512]
102417570  [KO:K06512]
102417755  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102417853  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
102417890  [KO:K06512]
102418507  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102418638  [KO:K06512]
102418838  [KO:K06512]
102419324  [KO:K02649]
102419342  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
102419381  IFNAR2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131]
102419469  [KO:K06512]
102419474  RELB; transcription factor RelB [KO:K09253]
102419580  [KO:K06512]
102419664  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
102419801  [KO:K06512]
102420000  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
102420500  [KO:K06463]
102421027  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102421207  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102421255  [KO:K06512]
102421777  ITGB3; integrin beta-3 [KO:K06493]
102422236  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102422347  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102422410  JUND; LOW QUALITY PROTEIN: transcription factor jun-D [KO:K04449]
102422436  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
102422535  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102422649  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102422734  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102422740  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
102422967  NCF1; neutrophil cytosol factor 1 [KO:K08011]
102423015  FOSL2; fos-related antigen 2 [KO:K09030]
102424236  RELA; transcription factor p65 [KO:K04735]
102424662  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102424919  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102424941  [KO:K06498]
102425292  [KO:K06472]
102425603  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102425721  NOX1; NADPH oxidase 1 [KO:K08008]
102425810  IRF9; interferon regulatory factor 9 [KO:K04693]
102426106  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102426303  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
102426307  NFKB2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
102426831  [KO:K08009]
102426867  IL1A; interleukin-1 alpha [KO:K04383]
102427077  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
102427189  IL1B; interleukin-1 beta [KO:K04519]
102427197  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
102427825  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
102427890  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102428391  MITF; microphthalmia-associated transcription factor isoform X2 [KO:K09455]
102428458  FOSB; protein fosB [KO:K09029]
102428507  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102428529  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102428803  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102428805  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
102428843  SYK; tyrosine-protein kinase SYK isoform X2 [KO:K05855] [EC:2.7.10.2]
102429105  CSF1; macrophage colony-stimulating factor 1 [KO:K05453]
102429230  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102429407  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
102429748  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102430192  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102430462  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
102430582  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102430852  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
102431228  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
102431488  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
102431742  CALCR; calcitonin receptor [KO:K04576]
102431888  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2 [KO:K06551]
102432210  [KO:K06551]
102432497  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102433176  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
102433506  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102433534  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102433673  GAB2; LOW QUALITY PROTEIN: GRB2-associated-binding protein 2 [KO:K08091]
102433832  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102434274  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102434410  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102434429  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
102435068  TGFB1; transforming growth factor beta-1 [KO:K13375]
102435667  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
102435748  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102435787  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
102435827  [KO:K06551]
102435832  BLNK; B-cell linker protein isoform X1 [KO:K07371]
102435895  TMEM64; transmembrane protein 64 [KO:K26770]
102436028  [KO:K06512]
102436137  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
102436804  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
102436955  [KO:K06512]
102437031  [KO:K04386]
102437415  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102437455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437558  TNF; tumor necrosis factor isoform X1 [KO:K03156]
102437564  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
102437567  [KO:K06512]
102437934  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102438079  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X3 [KO:K08601] [EC:3.4.19.12]
102438489  [KO:K06512]
102438684  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
102438792  [KO:K06512]
102438797  ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
102438914  [KO:K04441] [EC:2.7.11.24]
102438946  IFNG; interferon gamma [KO:K04687]
102439412  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
102439580  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
102439923  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102440031  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
102440354  [KO:K06512]
102440408  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102440810  [KO:K06512]
102441003  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102441064  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102441151  [KO:K06512]
102441209  NCF2; neutrophil cytosol factor 2 isoform X2 [KO:K08010]
102441522  [KO:K02649]
102441637  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
102441857  NFATC2; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
102442211  [KO:K06512]
102442319  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
102442353  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
102442443  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
102442528  [KO:K06512]
102442629  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
102442641  [KO:K06512]
102442760  [KO:K06512]
102442840  [KO:K06512]
102442861  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102442869  [KO:K06512]
102442951  [KO:K06512]
102443166  [KO:K06512]
102443221  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102443279  [KO:K04456] [EC:2.7.11.1]
106694413  [KO:K06512]
106694852  [KO:K06512]
106695123  [KO:K06512]
106695382  [KO:K06512]
111822992  [KO:K06551]
111823007  [KO:K06512]
111823988  [KO:K06512]
111823989  [KO:K06512]
111823991  [KO:K06512]
111824060  [KO:K06512]
111824061  [KO:K06512]
111824062  [KO:K06512]
111824063  [KO:K06512]
111824267  [KO:K06512]
111824268  [KO:K06512]
111824690  [KO:K06512]
111826193  [KO:K06551]
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
mlf04010  MAPK signaling pathway
mlf04020  Calcium signaling pathway
mlf04064  NF-kappa B signaling pathway
mlf04151  PI3K-Akt signaling pathway
mlf04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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