KEGG   PATHWAY: schu04350
Entry
schu04350                   Pathway                                
Name
TGF-beta signaling pathway - Siniperca chuatsi (mandarin fish)
Description
The transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species ranging from worms and insects to mammals. A wide spectrum of cellular functions such as proliferation, apoptosis, differentiation and migration are regulated by TGF-beta family members. TGF-beta family member binds to the Type II receptor and recruits Type I, whereby Type II receptor phosphorylates and activates Type I. The Type I receptor, in turn, phosphorylates receptor-activated Smads ( R-Smads: Smad1, Smad2, Smad3, Smad5, and Smad8). Once phosphorylated, R-Smads associate with the co-mediator Smad, Smad4, and the heteromeric complex then translocates into the nucleus. In the nucleus, Smad complexes activate specific genes through cooperative interactions with other DNA-binding and coactivator (or co-repressor) proteins.
Class
Environmental Information Processing; Signal transduction
Pathway map
schu04350  TGF-beta signaling pathway
schu04350

Other DBs
GO: 0007179
Organism
Siniperca chuatsi (mandarin fish) [GN:schu]
Gene
122879217  chrd; chordin [KO:K04657]
122869089  noggin-like [KO:K04658]
122867558  nog3; noggin-3 [KO:K04658]
122867893  nog2; noggin-2 [KO:K04658]
122884477  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
122863133  grem1a; gremlin-1a [KO:K23318]
122884369  grem2a; gremlin-2 [KO:K23318]
122861788  grem1b; gremlin-1 [KO:K23318]
122863142  thbs1b; thrombospondin-1 [KO:K16857]
122861455  thrombospondin-1-like [KO:K16857]
122871534  dcn; decorin [KO:K04660]
122883347  fmodb; fibromodulin [KO:K08121]
122867692  fmoda; fibromodulin a [KO:K08121]
122863682  lft1; lefty1 [KO:K04668]
122876558  fsta; follistatin-A isoform X1 [KO:K04661]
122863602  bmp2b; bone morphogenetic protein 2b [KO:K21283]
122879642  bmp16; bone morphogenetic protein 16 [KO:K21283]
122867609  bone morphogenetic protein 2-like [KO:K21283]
122887446  anti-dorsalizing morphogenic protein [KO:K21283]
122861887  bmp4; bone morphogenetic protein 4 [KO:K04662]
122866928  bmp6; bone morphogenetic protein 6 [KO:K16620]
122872036  inhibin beta B chain-like [KO:K22687]
122865460  inhibin beta B chain [KO:K22687]
122885489  inhbb; inhibin beta B chain [KO:K22687]
122886652  tfa; transferrin-a [KO:K14736]
122884621  bmp5; bone morphogenetic protein 5 [KO:K04663]
122888888  bone morphogenetic protein 7-like [KO:K16621]
122883595  bmp7b; bone morphogenetic protein 7b [KO:K16621]
122864445  bmp8a; bone morphogenetic protein 8A [KO:K16622]
122869726  gdf5; growth/differentiation factor 5 [KO:K04664]
122881911  gdf6a; growth/differentiation factor 6-A [KO:K20012]
122864785  gdf6b; growth/differentiation factor 6-B [KO:K20012]
122877619  amh; muellerian-inhibiting factor [KO:K04665]
122864206  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
122865443  thrombospondin type-1 domain-containing protein 4-like isoform X1 [KO:K23377]
122873275  adamtsl7; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
122873599  fbn1; fibrillin-1 [KO:K06825]
122884778  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
122879501  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
122880230  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
122880976  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
122863261  transforming growth factor beta-3 proprotein-like [KO:K13377]
122861438  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
122866481  inhbaa; inhibin subunit beta Aa [KO:K04667]
122887203  inhbab; inhibin subunit beta Ab [KO:K04667]
122876588  spaw; southpaw [KO:K04666]
122865455  nodal homolog 2-A-like [KO:K04666]
122867367  ndr2; nodal-related 2 [KO:K04666]
122884884  bone morphogenetic protein receptor type-1A-like isoform X1 [KO:K04673] [EC:2.7.11.30]
122875895  bmpr1ba; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
122865432  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform X1 [KO:K13578] [EC:2.7.11.30]
122862075  acvr1l; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
122885597  activin receptor type-1-like [KO:K04675] [EC:2.7.11.30]
122872292  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
122885291  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
122872371  activin receptor type-2A-like isoform X1 [KO:K04670] [EC:2.7.11.30]
122885386  acvr2aa; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
122881072  hjv; hemojuvelin [KO:K23100]
122874905  neo1a; neogenin 1a isoform X1 [KO:K06766]
122870110  tfr2; LOW QUALITY PROTEIN: transferrin receptor protein 2 [KO:K23910]
122887581  tfr1a; transferrin receptor 1a isoform X1 [KO:K06503]
122866882  tfr1b; transferrin receptor 1b isoform X1 [KO:K06503]
122877912  rgmd; RGM domain family, member D [KO:K23096]
122874386  rgma; repulsive guidance molecule A [KO:K23096]
122876432  rgmb; RGM domain family member B [KO:K06847]
122866616  tgfbr1b; TGF-beta receptor type-1b isoform X1 [KO:K04674] [EC:2.7.11.30]
122864473  TGF-beta receptor type-2-like isoform X1 [KO:K04388] [EC:2.7.11.30]
122885136  tgfbr2l; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
122881213  tgfbr2b; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
122883790  epithelial membrane protein 3-like [KO:K26257]
122886021  emp3a; epithelial membrane protein 3 [KO:K26257]
122887837  lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
122880493  transforming growth factor beta activator LRRC32-like [KO:K26316]
122866368  nrros; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
122883463  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
122867069  activin receptor type-1B-like [KO:K13567] [EC:2.7.11.30]
122866474  acvr2ba; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
122887024  activin receptor type-2B-like [KO:K13596] [EC:2.7.11.30]
122885598  activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
122866891  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
122873682  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
122879846  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
122888167  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
122877070  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
122862259  smad3a; mothers against decapentaplegic homolog 3a isoform X1 [KO:K23605]
122875137  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
122876696  mothers against decapentaplegic homolog 4 [KO:K04501]
122863799  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
122865489  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
122863684  mothers against decapentaplegic homolog 6-like [KO:K04677]
122875136  smad6b; mothers against decapentaplegic homolog 6b isoform X1 [KO:K04677]
122865468  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
122869410  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
122873896  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
122877480  zfyve9b; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
122865382  zfyve16; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 16 [KO:K04679]
122887099  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
122868958  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
122866431  cullin-1 [KO:K03347]
122888513  skp1; S-phase kinase-associated protein 1 [KO:K03094]
122876093  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122882438  rho-related GTP-binding protein RhoA-D [KO:K04513]
122882439  rho-related GTP-binding protein RhoA-C-like [KO:K04513]
122883454  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
122883743  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
122884474  transforming protein RhoA [KO:K04513]
122884762  rho-related GTP-binding protein RhoA-D-like [KO:K04513]
122886396  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
122879564  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
122876785  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
122888512  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
122879960  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like isoform X1 [KO:K04382] [EC:3.1.3.16]
122888190  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122878761  rps6kb1b; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
122873242  ribosomal protein S6 kinase beta-2-like isoform X1 [KO:K04688] [EC:2.7.11.1]
122881776  hepcidin-1 [KO:K23106]
122881038  hepcidin-like [KO:K23106]
122881039  hepcidin-like [KO:K23106]
122865104  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
122861911  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
122862680  DNA-binding protein inhibitor ID-2-like [KO:K17693]
122861496  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
122881536  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
122869943  rbl1; retinoblastoma-like protein 1 [KO:K04681]
122880440  retinoblastoma-like protein 2 isoform X1 [KO:K04681]
122887627  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
122879475  transcription factor E2F4-like [KO:K04682]
122874765  e2f4; transcription factor E2F4 isoform X1 [KO:K04682]
122885407  transcription factor Dp-1-like [KO:K04683]
122868808  LOW QUALITY PROTEIN: CREB-binding protein-like [KO:K04498] [EC:2.3.1.48]
122869593  ep300b; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
122873931  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
122867407  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
122863200  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
122887612  skila; ski-like protein [KO:K18499]
122863611  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
122882836  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
122874248  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
122874799  paired amphipathic helix protein Sin3a-like isoform X1 [KO:K11644]
122862440  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
122862912  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
122865060  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
122888109  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
122866758  tgif1; homeobox protein TGIF1 [KO:K19383]
122866331  myca; transcriptional regulator Myc-A isoform X1 [KO:K04377]
122886971  transcriptional regulator Myc-2-like isoform X1 [KO:K04377]
122872953  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122880519  pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
Compound
C14819  Fe3+
Reference
PMID:12809600
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:14534577
  Authors
Derynck R, Zhang YE.
  Title
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
  Journal
Nature 425:577-84 (2003)
DOI:10.1038/nature02006
Reference
PMID:11252892
  Authors
Massague J.
  Title
How cells read TGF-beta signals.
  Journal
Nat Rev Mol Cell Biol 1:169-78 (2000)
DOI:10.1038/35043051
Reference
PMID:14557817
  Authors
Siegel PM, Massague J.
  Title
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
  Journal
Nat Rev Cancer 3:807-21 (2003)
DOI:10.1038/nrc1208
Reference
PMID:14769828
  Authors
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
  Title
The bone morphogenetic protein system in mammalian reproduction.
  Journal
Endocr Rev 25:72-101 (2004)
DOI:10.1210/er.2003-0007
Reference
PMID:11252746
  Authors
De Robertis EM, Larrain J, Oelgeschlager M, Wessely O.
  Title
The establishment of Spemann's organizer and patterning of the vertebrate embryo.
  Journal
Nat Rev Genet 1:171-81 (2000)
DOI:10.1038/35042039
Reference
PMID:12163231
  Authors
Gumienny TL, Padgett RW.
  Title
The other side of TGF-beta superfamily signal regulation: thinking outside the cell.
  Journal
Trends Endocrinol Metab 13:295-9 (2002)
DOI:10.1016/S1043-2760(02)00615-X
Reference
PMID:11836504
  Authors
Hamada H, Meno C, Watanabe D, Saijoh Y.
  Title
Establishment of vertebrate left-right asymmetry.
  Journal
Nat Rev Genet 3:103-13 (2002)
DOI:10.1038/nrg732
Reference
PMID:12466190
  Authors
Chang H, Brown CW, Matzuk MM.
  Title
Genetic analysis of the mammalian transforming growth factor-beta superfamily.
  Journal
Endocr Rev 23:787-823 (2002)
DOI:10.1210/er.2002-0003
Reference
PMID:10021351
  Authors
Morita K, Chow KL, Ueno N.
  Title
Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family.
  Journal
Development 126:1337-47 (1999)
Reference
PMID:9847239
  Authors
Krishna S, Maduzia LL, Padgett RW.
  Title
Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans.
  Journal
Development 126:251-60 (1999)
Reference
PMID:15063168
  Authors
Chen Y, Mironova E, Whitaker LL, Edwards L, Yost HJ, Ramsdell AF.
  Title
ALK4 functions as a receptor for multiple TGF beta-related ligands to regulate left-right axis determination and mesoderm induction in Xenopus.
  Journal
Dev Biol 268:280-94 (2004)
DOI:10.1016/j.ydbio.2003.12.035
Reference
PMID:10519551
  Authors
Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J, Niehrs C
  Title
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
  Journal
Nature 401:480-5 (1999)
DOI:10.1038/46794
Reference
PMID:19758997
  Authors
Yan X, Lin Z, Chen F, Zhao X, Chen H, Ning Y, Chen YG
  Title
Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling.
  Journal
J Biol Chem 284:30097-104 (2009)
DOI:10.1074/jbc.M109.049304
Reference
PMID:8093006
  Authors
Hildebrand A, Romaris M, Rasmussen LM, Heinegard D, Twardzik DR, Border WA, Ruoslahti E
  Title
Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.
  Journal
Biochem J 302 ( Pt 2):527-34 (1994)
DOI:10.1042/bj3020527
Reference
PMID:10934147
  Authors
Soo C, Hu FY, Zhang X, Wang Y, Beanes SR, Lorenz HP, Hedrick MH, Mackool RJ, Plaas A, Kim SJ, Longaker MT, Freymiller E, Ting K
  Title
Differential expression of fibromodulin, a transforming growth factor-beta modulator, in fetal skin development and scarless repair.
  Journal
Am J Pathol 157:423-33 (2000)
DOI:10.1016/s0002-9440(10)64555-5
Reference
PMID:16642010
  Authors
Anderson GJ, Frazer DM
  Title
Iron metabolism meets signal transduction.
  Journal
Nat Genet 38:503-4 (2006)
DOI:10.1038/ng0506-503
Reference
PMID:26735394
  Authors
Canali S, Core AB, Zumbrennen-Bullough KB, Merkulova M, Wang CY, Schneyer AL, Pietrangelo A, Babitt JL
  Title
Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice.
  Journal
Endocrinology 157:1146-62 (2016)
DOI:10.1210/en.2015-1747
Reference
PMID:26160612
  Authors
Ganz T, Nemeth E
  Title
Iron homeostasis in host defence and inflammation.
  Journal
Nat Rev Immunol 15:500-10 (2015)
DOI:10.1038/nri3863
Reference
PMID:15975920
  Authors
Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, Lin HY
  Title
Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor.
  Journal
J Biol Chem 280:29820-7 (2005)
DOI:10.1074/jbc.M503511200
Reference
PMID:15671031
  Authors
Samad TA, Rebbapragada A, Bell E, Zhang Y, Sidis Y, Jeong SJ, Campagna JA, Perusini S, Fabrizio DA, Schneyer AL, Lin HY, Brivanlou AH, Attisano L, Woolf CJ
  Title
DRAGON, a bone morphogenetic protein co-receptor.
  Journal
J Biol Chem 280:14122-9 (2005)
DOI:10.1074/jbc.M410034200
Reference
PMID:33925597
  Authors
Vogt AS, Arsiwala T, Mohsen M, Vogel M, Manolova V, Bachmann MF
  Title
On Iron Metabolism and Its Regulation.
  Journal
Int J Mol Sci 22:ijms22094591 (2021)
DOI:10.3390/ijms22094591
Reference
PMID:20495575
  Authors
Ikushima H, Miyazono K
  Title
TGFbeta signalling: a complex web in cancer progression.
  Journal
Nat Rev Cancer 10:415-24 (2010)
DOI:10.1038/nrc2853
Related
pathway
schu04010  MAPK signaling pathway
schu04110  Cell cycle
schu04120  Ubiquitin mediated proteolysis
schu04210  Apoptosis
KO pathway
ko04350   
LinkDB

DBGET integrated database retrieval system