KEGG   PATHWAY: xco04350
Entry
xco04350                    Pathway                                
Name
TGF-beta signaling pathway - Xiphophorus couchianus (Monterrey platyfish)
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
xco04350  TGF-beta signaling pathway
xco04350

Other DBs
GO: 0007179
Organism
Xiphophorus couchianus (Monterrey platyfish) [GN:xco]
Gene
114161982  chrd; chordin [KO:K04657]
114151703  noggin-3-like [KO:K04658]
114159512  noggin-like [KO:K04658]
114135355  noggin-2-like [KO:K04658]
114136124  nbl1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
114159056  gremlin-1-like [KO:K23318]
114138190  grem2; gremlin-2 [KO:K23318]
114133994  gremlin-1-like [KO:K23318]
114158629  thrombospondin-1-like [KO:K16857]
114134229  thrombospondin-1-like [KO:K16857]
114160800  dcn; decorin [KO:K04660]
114136217  fibromodulin-like [KO:K08121]
114159042  left-right determination factor 2-like [KO:K04668]
114154714  fst; follistatin isoform X1 [KO:K04661]
114133430  bone morphogenetic protein 2-like [KO:K21283]
114158609  bmp2; bone morphogenetic protein 2 [KO:K21283]
114147081  bone morphogenetic protein 2-like [KO:K21283]
114134479  bmp4; bone morphogenetic protein 4 [KO:K04662]
114136539  bmp6; bone morphogenetic protein 6 [KO:K16620]
114147900  inhibin beta B chain-like [KO:K22687]
114136097  inhibin beta B chain-like [KO:K22687]
114140597  inhibin beta B chain-like [KO:K22687]
114146899  serotransferrin-like [KO:K14736]
114138152  bmp5; bone morphogenetic protein 5 [KO:K04663]
114143534  bmp7; bone morphogenetic protein 7 [KO:K16621]
114135903  bone morphogenetic protein 7-like isoform X1 [KO:K16621]
114155448  bmp8a; bone morphogenetic protein 8A [KO:K16622]
114136056  gdf5; growth/differentiation factor 5 [KO:K04664]
114143856  growth/differentiation factor 6-A-like [KO:K20012]
114151005  LOW QUALITY PROTEIN: muellerian-inhibiting factor-like [KO:K04665]
114156470  tumor necrosis factor-like isoform X1 [KO:K03156]
114143584  thsd4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
114142632  fbn1; fibrillin-1 [KO:K06825]
114137718  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
114161405  transforming growth factor beta-1 proprotein-like [KO:K13375]
114139436  transforming growth factor beta-2 proprotein-like [KO:K13376]
114158174  transforming growth factor beta-3 proprotein-like [KO:K13377]
114134077  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
114146504  inhibin beta A chain-like [KO:K04667]
114137052  inhibin beta A chain-like [KO:K04667]
114150206  nodal homolog 2-A-like [KO:K04666]
114155136  nodal homolog [KO:K04666]
114151802  nodal; nodal homolog [KO:K04666]
114138037  bmpr1a; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
114154918  bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
114149477  bone morphogenetic protein receptor type-1B-like [KO:K13578] [EC:2.7.11.30]
114148164  acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
114134098  activin receptor type-1-like [KO:K04675] [EC:2.7.11.30]
114144944  activin receptor type-1-like [KO:K04675] [EC:2.7.11.30]
114148757  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
114140973  bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
114147517  activin receptor type-2A-like isoform X1 [KO:K04670] [EC:2.7.11.30]
114141013  acvr2a; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
114141630  hemojuvelin-like [KO:K23100]
114142956  neo1; neogenin isoform X1 [KO:K06766]
114140540  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
114147191  tfrc; transferrin receptor protein 1 [KO:K06503]
114136987  transferrin receptor protein 1-like isoform X1 [KO:K06503]
114157031  rgma; repulsive guidance molecule A [KO:K23096]
114151251  repulsive guidance molecule A-like [KO:K23096]
114154383  rgmb; RGM domain family member B [KO:K06847]
114149782  TGF-beta receptor type-1-like isoform X1 [KO:K04674] [EC:2.7.11.30]
114145015  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
114156140  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
114136297  epithelial membrane protein 3-like [KO:K26257]
114141538  epithelial membrane protein 3-like isoform X1 [KO:K26257]
114153230  lrrc32; LOW QUALITY PROTEIN: transforming growth factor beta activator LRRC32 [KO:K26316]
114139320  transforming growth factor beta activator LRRC33-like [KO:K26316]
114137155  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
114143630  acvr1b; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
114146822  activin receptor type-2B-like [KO:K13596] [EC:2.7.11.30]
114136607  activin receptor type-2B-like [KO:K13596] [EC:2.7.11.30]
114147496  acvr1c; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
114137072  bambi; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
114144989  smad1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
114139311  mothers against decapentaplegic homolog 5 [KO:K16790]
114153305  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
114155259  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
114156401  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
114142996  mothers against decapentaplegic homolog 3 [KO:K23605]
114154836  mothers against decapentaplegic homolog 4-like [KO:K04501]
114149415  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
114141666  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
114143577  mothers against decapentaplegic homolog 6-like isoform X1 [KO:K04677]
114158665  smad6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
114149728  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
114159764  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
114159826  E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
114144713  E3 ubiquitin-protein ligase SMURF2-like isoform X1 [KO:K04678] [EC:2.3.2.26]
114149461  zinc finger FYVE domain-containing protein 16-like [KO:K04679]
114146962  zfyve9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
114150756  zinc finger FYVE domain-containing protein 9-like isoform X1 [KO:K04679]
114160562  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
114136425  cul1; cullin-1 [KO:K03347]
114152468  skp1; S-phase kinase-associated protein 1 [KO:K03094]
114160039  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
114154145  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114153166  rho-related GTP-binding protein RhoA-D isoform X1 [KO:K04513]
114153549  transforming protein RhoA-like [KO:K04513]
114144101  rho-related GTP-binding protein RhoA-B-like [KO:K04513]
114142532  rho-related GTP-binding protein RhoA-C [KO:K04513]
114135208  transforming protein RhoA [KO:K04513]
114146483  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
114161548  ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
114144578  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
114152467  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
114138792  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
114144564  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
114161868  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
114153064  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
114144881  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
114143942  hepcidin-like [KO:K23106]
114139183  hamp; hepcidin [KO:K23106]
114135984  DNA-binding protein inhibitor ID-1-like [KO:K04680]
114134655  DNA-binding protein inhibitor ID-3-A-like [KO:K17694]
114145162  DNA-binding protein inhibitor ID-4-like [KO:K17695]
114143740  rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K04681]
114136244  rbl1; retinoblastoma-like protein 1 [KO:K04681]
114146937  transcription factor E2F5-like [KO:K04682]
114143743  transcription factor E2F4-like [KO:K04682]
114152335  e2f4; transcription factor E2F4 [KO:K04682]
114148530  tfdp1; transcription factor Dp-1 [KO:K04683]
114160081  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
114144407  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
114151812  histone acetyltransferase p300-like isoform X1 [KO:K04498] [EC:2.3.1.48]
114160057  histone acetyltransferase p300-like isoform X1 [KO:K04498] [EC:2.3.1.48]
114134954  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
114146565  skil; ski-like protein [KO:K18499]
114141933  ski; ski oncogene [KO:K26503]
114135076  ski oncogene-like [KO:K26503]
114143076  paired amphipathic helix protein Sin3a-like isoform X1 [KO:K11644]
114159091  sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
114159004  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
114155738  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
114134136  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
114152811  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
114136651  homeobox protein AKR-like isoform X1 [KO:K19383]
114135164  proline-rich protein 36-like [KO:K19553]
114136008  transcriptional regulator Myc-2-like [KO:K04377]
114137130  myc; myc proto-oncogene protein isoform X1 [KO:K04377]
114146318  transcriptional regulator Myc-like isoform X1 [KO:K04377]
114144722  cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
114139492  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
xco04010  MAPK signaling pathway
xco04110  Cell cycle
xco04120  Ubiquitin mediated proteolysis
xco04210  Apoptosis
KO pathway
ko04350   
LinkDB

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