KEGG   PATHWAY: pov04350
Entry
pov04350                    Pathway                                
Name
TGF-beta signaling pathway - Paralichthys olivaceus (Japanese flounder)
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
pov04350  TGF-beta signaling pathway
pov04350

Other DBs
GO: 0007179
Organism
Paralichthys olivaceus (Japanese flounder) [GN:pov]
Gene
109645473  chrd; chordin [KO:K04657]
109645927  nog; noggin [KO:K04658]
109634220  noggin-like [KO:K04658]
109646262  noggin-2-like [KO:K04658]
109627680  noggin-like [KO:K04658]
109642732  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
109632643  grem2; gremlin-2 [KO:K23318]
109628191  gremlin-1-like [KO:K23318]
109636147  grem1; gremlin-1 [KO:K23318]
109627896  thrombospondin-1-like [KO:K16857]
109636170  thrombospondin-1-like [KO:K16857]
109632778  decorin-like [KO:K04660]
109629079  lumican-like [KO:K08121]
109629307  fibromodulin-like [KO:K08121]
109635113  fmod; fibromodulin [KO:K08121]
109632454  left-right determination factor 2-like [KO:K04668]
109637161  fst; follistatin isoform X1 [KO:K04661]
109626981  bone morphogenetic protein 2-like [KO:K21283]
109632388  bmp2; bone morphogenetic protein 2 [KO:K21283]
109629970  bone morphogenetic protein 2-like [KO:K21283]
109637197  bone morphogenetic protein 2-like [KO:K21283]
109646622  bmp4; bone morphogenetic protein 4 [KO:K04662]
109629656  bmp6; bone morphogenetic protein 6 [KO:K16620]
109635534  inhibin beta B chain-like isoform X1 [KO:K22687]
109645552  inhibin beta B chain-like [KO:K22687]
109637318  inhibin beta B chain-like [KO:K22687]
109640062  serotransferrin [KO:K14736]
109631152  bmp5; bone morphogenetic protein 5 [KO:K04663]
109635082  bmp7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
109643221  bone morphogenetic protein 7-like [KO:K16621]
109643319  bone morphogenetic protein 8A-like [KO:K16622]
109646851  gdf5; growth/differentiation factor 5 [KO:K04664]
109643823  growth/differentiation factor 6-B-like [KO:K20012]
109631977  gdf6; growth/differentiation factor 6 isoform X1 [KO:K20012]
109625611  amh; muellerian-inhibiting factor [KO:K04665]
109640782  tumor necrosis factor-like [KO:K03156]
109637773  thrombospondin type-1 domain-containing protein 4-like isoform X1 [KO:K23377]
109624789  thsd4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
109637254  fbn1; fibrillin-1 [KO:K06825]
109630437  ltbp1; latent-transforming growth factor beta-binding protein 1 [KO:K19559]
109630415  transforming growth factor beta-1-like [KO:K13375]
109642431  transforming growth factor beta-2-like [KO:K13376]
109631969  tgfb2; transforming growth factor beta-2 [KO:K13376]
109628154  tgfb3; transforming growth factor beta-3 [KO:K13377]
109636158  transforming growth factor beta-3-like [KO:K13377]
109642717  inhibin beta A chain-like [KO:K04667]
109643354  inhibin beta A chain-like [KO:K04667]
109626995  nodal; nodal homolog [KO:K04666]
109626088  nodal homolog [KO:K04666]
109638187  nodal homolog [KO:K04666]
109641990  bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
109626287  bone morphogenetic protein receptor type-1B-like isoform X1 [KO:K13578] [EC:2.7.11.30]
109638193  bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
109636415  activin receptor type-1-like isoform X1 [KO:K04675] [EC:2.7.11.30]
109631350  acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
109646787  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
109642017  activin receptor type-2A-like [KO:K04670] [EC:2.7.11.30]
109639027  acvr2a; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
109644292  hemojuvelin-like [KO:K23100]
109637265  neo1; neogenin isoform X1 [KO:K06766]
109639640  transferrin receptor protein 1-like [KO:K06503]
109641300  tfrc; transferrin receptor protein 1 [KO:K06503]
109625878  RGM domain family member B-like [KO:K23096]
109624531  rgma; repulsive guidance molecule A [KO:K23096]
109638054  RGM domain family member B-like [KO:K06847]
109638437  TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
109631953  TGF-beta receptor type-2-like isoform X1 [KO:K04388] [EC:2.7.11.30]
109647461  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
109639132  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
109638604  epithelial membrane protein 3-like [KO:K26257]
109630630  epithelial membrane protein 3-like [KO:K26257]
109640890  leucine-rich repeat-containing protein 32-like isoform X1 [KO:K26316]
109628184  negative regulator of reactive oxygen species-like isoform X1 [KO:K26316]
109629499  negative regulator of reactive oxygen species-like [KO:K26317]
109630841  activin receptor type-1B-like [KO:K13567] [EC:2.7.11.30]
109629242  activin receptor type-1B-like isoform X1 [KO:K13567] [EC:2.7.11.30]
109646928  acvr2b; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
109631050  acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
109629852  bambi; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
109638377  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
109626568  mothers against decapentaplegic homolog 5 [KO:K16790]
109635806  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
109633657  mothers against decapentaplegic homolog 2-like [KO:K04500]
109626315  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
109637282  mothers against decapentaplegic homolog 3 [KO:K23605]
109624649  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
109642417  mothers against decapentaplegic homolog 4 [KO:K04501]
109626289  mothers against decapentaplegic homolog 4-like [KO:K04501]
109641002  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
109643214  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
109624325  smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
109626543  smad7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
109627350  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109641545  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109644866  E3 ubiquitin-protein ligase SMURF2-like [KO:K04678] [EC:2.3.2.26]
109642570  zinc finger FYVE domain-containing protein 9-like [KO:K04679]
109625347  zinc finger FYVE domain-containing protein 9-like [KO:K04679]
109626323  zinc finger FYVE domain-containing protein 16-like [KO:K04679]
109646981  zfyve9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
109643626  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109645364  cul1; cullin-1 [KO:K03347]
109635809  skp1; S-phase kinase-associated protein 1 [KO:K03094]
109639504  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
109640677  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109638588  transforming protein RhoA [KO:K04513]
109630779  rho-related GTP-binding protein RhoA-B [KO:K04513]
109635208  rho-related GTP-binding protein RhoA-C-like [KO:K04513]
109642611  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
109630286  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109643848  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
109628717  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109627373  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
109628582  rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
109643323  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
109632102  hepcidin-like [KO:K23106]
109633143  hamp; hepcidin [KO:K23106]
109647642  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
109627801  id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
109628157  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
109631923  DNA-binding protein inhibitor ID-4-like [KO:K17695]
109624795  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K04681]
109645359  rbl1; retinoblastoma-like protein 1 [KO:K04681]
109637755  transcription factor E2F5-like [KO:K04682]
109624347  e2f4; transcription factor E2F4 [KO:K04682]
109636836  transcription factor E2F5-like [KO:K04682]
109631414  tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
109627429  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109643520  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
109626906  histone acetyltransferase p300-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109638720  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
109635527  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
109644790  skil; ski-like protein [KO:K18499]
109639664  ski; ski oncogene [KO:K26503]
109648157  ski oncogene-like [KO:K26503]
109624472  sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
109643187  paired amphipathic helix protein Sin3a-like isoform X1 [KO:K11644]
109632588  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
109631851  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
109628055  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
109628545  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
109629880  homeobox protein AKR-like [KO:K19383]
109629330  flocculation protein FLO11-like [KO:K19553]
109629885  myc; myc proto-oncogene protein [KO:K04377]
109642921  transcriptional regulator Myc-2-like [KO:K04377]
109638248  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
109623986  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
pov04010  MAPK signaling pathway
pov04110  Cell cycle
pov04120  Ubiquitin mediated proteolysis
pov04210  Apoptosis
KO pathway
ko04350   
LinkDB

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