KEGG   PATHWAY: mdt04380
Entry
mdt04380                    Pathway                                
Name
Osteoclast differentiation - Myotis daubentonii (Daubenton's 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
mdt04380  Osteoclast differentiation
mdt04380

Other DBs
GO: 0030316
Organism
Myotis daubentonii (Daubenton's bat) [GN:mdt]
Gene
132211282  CALCR; calcitonin receptor [KO:K04576]
132211786  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
132212192  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
132212630  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
132212752  IFNB1; interferon beta [KO:K05415]
132212793  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
132212977  IL1R1; LOW QUALITY PROTEIN: interleukin-1 receptor type 1 [KO:K04386]
132212992  FHL2; four and a half LIM domains protein 2 isoform X1 [KO:K14380]
132213109  IL1A; interleukin-1 alpha [KO:K04383]
132213110  IL1B; interleukin-1 beta [KO:K04519]
132213277  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
132213524  FOSL2; fos-related antigen 2 isoform X1 [KO:K09030]
132214177  BLNK; B-cell linker protein isoform X1 [KO:K07371]
132214229  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
132214277  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
132214715  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
132214826  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
132215204  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
132215431  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
132215517  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132215631  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
132215694  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
132215747  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
132215779  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
132216495  [KO:K06512]
132216496  [KO:K06512]
132216499  [KO:K06512]
132216500  [KO:K06512]
132216501  [KO:K06512]
132216508  [KO:K06512]
132216515  [KO:K06512]
132216517  [KO:K06512]
132216518  [KO:K06512]
132216520  [KO:K06512]
132216521  [KO:K06512]
132216522  [KO:K06512]
132216523  [KO:K06512]
132216524  [KO:K06512]
132216525  [KO:K06512]
132216526  [KO:K06512]
132216527  [KO:K06512]
132216528  [KO:K06512]
132216529  [KO:K06512]
132216542  OSCAR; osteoclast-associated immunoglobulin-like receptor isoform X1 [KO:K14377]
132216708  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
132216726  FOSB; protein FosB isoform X1 [KO:K09029]
132216748  RELB; transcription factor RelB isoform X1 [KO:K09253]
132216839  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
132216889  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132216971  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
132217017  [KO:K04392]
132217089  [KO:K08009]
132217153  [KO:K06512]
132217159  [KO:K06512]
132217215  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
132217247  [KO:K06512]
132217248  [KO:K06512]
132217249  [KO:K06512]
132217251  [KO:K06512]
132217256  [KO:K06512]
132217257  [KO:K06512]
132217258  [KO:K06512]
132217259  [KO:K06512]
132217595  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
132218191  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
132218548  ITGB3; integrin beta-3 [KO:K06493]
132218783  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
132219031  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
132219091  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
132219167  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
132219468  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
132219584  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
132220093  TMEM64; transmembrane protein 64 [KO:K26770]
132220276  NCF2; neutrophil cytosol factor 2 [KO:K08010]
132220311  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b isoform X1 [KO:K12560]
132220440  [KO:K06472]
132220529  [KO:K06463]
132220571  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
132220677  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
132220680  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
132222012  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
132222289  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
132222407  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
132222581  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
132223978  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
132224109  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
132226175  IFNG; interferon gamma [KO:K04687]
132226843  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
132226858  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
132226940  [KO:K04403]
132227018  NCF4; neutrophil cytosol factor 4 isoform X1 [KO:K08012]
132227181  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
132227391  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
132227766  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
132228392  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
132228444  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
132228611  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
132229835  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
132229838  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
132229839  IFNGR2; interferon gamma receptor 2 [KO:K05133]
132230128  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132230981  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
132231012  JUN; transcription factor Jun [KO:K04448]
132231240  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
132231259  FOS; protein c-Fos [KO:K04379]
132231371  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
132231710  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
132232782  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
132232806  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
132233085  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
132233172  NCF1; neutrophil cytosol factor 1 [KO:K08011]
132233368  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
132233575  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
132234600  SQSTM1; sequestosome-1 [KO:K14381]
132234601  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
132234607  [KO:K04456] [EC:2.7.11.1]
132234663  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
132234728  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
132234808  JUND; transcription factor JunD [KO:K04449]
132234815  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
132234912  JUNB; transcription factor JunB [KO:K09028]
132235015  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
132235064  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
132235370  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
132235845  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
132235951  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
132236015  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
132236583  TNF; tumor necrosis factor [KO:K03156]
132236801  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
132236928  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
132236985  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
132237065  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
132237348  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
132237408  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
132237411  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
132237456  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
132238061  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
132238165  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
132239239  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
132239440  [KO:K06551]
132239443  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1 [KO:K06551]
132239445  [KO:K06551]
132239447  [KO:K06551]
132239653  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
132239710  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
132240747  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
132240857  IRF9; interferon regulatory factor 9 [KO:K04693]
132241195  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
132241254  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
132241397  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
132241412  RELA; transcription factor p65 isoform X1 [KO:K04735]
132241763  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
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
mdt04010  MAPK signaling pathway
mdt04020  Calcium signaling pathway
mdt04064  NF-kappa B signaling pathway
mdt04151  PI3K-Akt signaling pathway
mdt04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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