KEGG   PATHWAY: dre04350
Entry
dre04350                    Pathway                                
Name
TGF-beta signaling pathway - Danio rerio (zebrafish)
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
dre04350  TGF-beta signaling pathway
dre04350

Other DBs
GO: 0007179
Organism
Danio rerio (zebrafish) [GN:dre]
Gene
100002201  grem2a; gremlin-2 [KO:K23318]
100004116  fsta; follistatin-A precursor [KO:K04661]
100005449  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X2 [KO:K04679]
100005728  grem1b; gremlin-1 [KO:K23318]
100006041  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
100007184  nog5; noggin 5 precursor [KO:K04658]
100007653  skila; ski-like protein [KO:K18499]
100148867  lrrc32; transforming growth factor beta activator LRRC32 [KO:K26316]
100149664  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform 2 precursor [KO:K13578] [EC:2.7.11.30]
100151181  smad10b; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
100170835  skilb; SKI-like proto-oncogene b [KO:K18499]
100329171  bmp16; bone morphogenetic protein 16 precursor [KO:K21283]
100329520  [KO:K22687]
100329779  rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
100330961  fbn1; fibrillin-1 [KO:K06825]
100331014  acvr2ab; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
100331105  acvr1c; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
100331938  [KO:K13596] [EC:2.7.11.30]
100332237  thbs1a; thrombospondin-1 [KO:K16857]
100332300  [KO:K23318]
100332721  neo1b; neogenin isoform X1 [KO:K06766]
100332902  [KO:K22687]
100334210  gdf5; growth/differentiation factor 5 [KO:K04664]
100535338  [KO:K19553]
101882992  zfyve9b; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
101887111  [KO:K22687]
116992  smad6a; mothers against decapentaplegic homolog 6a [KO:K04677]
140619  admp; anti-dorsalizing morphogenic protein precursor [KO:K21283]
192302  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
246093  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
266599  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
266983  neo1a; neogenin 1a isoform 2 precursor [KO:K06766]
30072  inhbaa; inhibin subunit beta Aa [KO:K04667]
30101  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
30113  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
30145  lft1; lefty1 precursor [KO:K04668]
30146  lft2; lefty2 precursor [KO:K04668]
30161  chrd; chordin precursor [KO:K04657]
30164  pitx2; pituitary homeobox 2 [KO:K04686]
30173  nog3; noggin-3 precursor [KO:K04658]
30174  nog1; noggin-1 precursor [KO:K04658]
30180  gdf6b; growth/differentiation factor 6-B precursor [KO:K20012]
30183  acvr1ba; activin A receptor type 1Ba precursor [KO:K13567] [EC:2.7.11.30]
30185  nog2; noggin-2 precursor [KO:K04658]
30255  tfa; transferrin-a precursor [KO:K14736]
30275  inhbb; inhibin beta B chain precursor [KO:K22687]
30457  acvr2ba; activin receptor type-2B precursor [KO:K13596] [EC:2.7.11.30]
30493  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
30584  bmp7a; bone morphogenetic protein 7a precursor [KO:K16621]
30612  bmp4; bone morphogenetic protein 4 precursor [KO:K04662]
30615  acvr1l; activin receptor type-1 precursor [KO:K04675] [EC:2.7.11.30]
30628  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
30631  bmp2a; bone morphogenetic protein 2 precursor [KO:K21283]
30632  bmp2b; bone morphogenetic protein 2b precursor [KO:K21283]
30639  smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
30641  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
30642  gdf7; growth/differentiation factor 7 [KO:K20013]
30686  myca; transcriptional regulator Myc-A [KO:K04377]
30739  tgfbr2b; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
30742  bmpr1ba; bone morphogenetic protein receptor type-1B precursor [KO:K13578] [EC:2.7.11.30]
321364  id2b; DNA-binding protein inhibitor ID-2b [KO:K17693]
321695  smurf1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
321756  tgif1; homeobox protein TGIF1 [KO:K19383]
321842  rgmd; RGM domain family, member D precursor [KO:K23096]
321932  hjv; hemojuvelin precursor [KO:K23100]
323346  sin3ab; paired amphipathic helix protein Sin3a isoform X2 [KO:K11644]
323883  cul1a; cullin-1a [KO:K03347]
324109  sp1; transcription factor Sp1 [KO:K04684]
326282  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
326283  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
338101  spaw; southpaw precursor [KO:K04666]
359834  tgfb1a; transforming growth factor, beta 1a precursor [KO:K13375]
360144  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
369194  tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
369195  tgfb3; transforming growth factor beta-3 proprotein precursor [KO:K13377]
393141  mycb; transcriptional regulator Myc-B [KO:K04377]
393246  ncor1; nuclear receptor corepressor 1 [KO:K04650]
393716  skp1; S-phase kinase-associated protein 1 [KO:K03094]
393749  tfdp1b; transcription factor Dp-1b [KO:K04683]
393885  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
394026  bmp5; bone morphogenetic protein 5 precursor [KO:K04663]
399480  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
402837  hamp; hepcidin-1 isoform 1 precursor [KO:K23106]
402908  e2f5; transcription factor E2F5 isoform 1 [KO:K04682]
404629  nbl1; neuroblastoma suppressor of tumorigenicity 1 precursor [KO:K19558]
405778  grem1a; gremlin-1a precursor [KO:K23318]
405785  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
405790  ifng1; interferon gamma 1 precursor [KO:K04687]
406349  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
406411  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
406582  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
406659  rhoac; rho-related GTP-binding protein RhoA-C [KO:K04513]
406685  ppp2r1ba; protein phosphatase 2, regulatory subunit A, beta a [KO:K03456]
406741  e2f4; transcription factor E2F4 [KO:K04682]
406813  tfdp1a; transcription factor Dp-1a [KO:K04683]
406816  cul1b; cullin-1b [KO:K03347]
414272  rgma; repulsive guidance molecule A [KO:K23096]
414273  rgmb; repulsive guidance molecule B precursor [KO:K06847]
431736  bambib; BMP and activin membrane-bound inhibitor homolog (Xenopus laevis) b precursor [KO:K10162]
436718  rhocb; rho-related GTP-binding protein RhoA-D [KO:K04513]
436910  tmem53; transmembrane protein 53 [KO:K28359]
445318  nrros; transforming growth factor beta activator LRRC33 precursor [KO:K26317]
445564  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
447846  bmpr1ab; bone morphogenetic protein receptor, type IAb precursor [KO:K04673] [EC:2.7.11.30]
449548  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
449846  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
493624  amh; muellerian-inhibiting factor precursor [KO:K04665]
494476  tfr2; transferrin receptor protein 2 [KO:K23910]
494477  tfr1a; transferrin receptor 1a [KO:K06503]
494478  tfr1b; transferrin receptor 1b [KO:K06503]
503761  bmp6; bone morphogenetic protein 6 precursor [KO:K16620]
550399  grem2b; gremlin-2b precursor [KO:K23318]
550585  ppp2caa; protein phosphatase 2 catalytic subunit alpha a [KO:K04382] [EC:3.1.3.16]
553359  acvr2aa; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
553816  inhbab; inhibin subunit beta Ab precursor [KO:K04667]
555655  bmpr2b; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
556634  adamtsl7; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
557567  bmp7b; bone morphogenetic protein 7b precursor [KO:K16621]
558474  lemd3; inner nuclear membrane protein Man1 [KO:K19410]
559111  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
559222  acvr1bb; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
559273  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
559723  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
560317  smad10a; uncharacterized protein LOC560317 isoform 2 [KO:K04501]
560446  tgfbr2l; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
560578  tgfbr1a; TGF-beta receptor type-1a precursor [KO:K04674] [EC:2.7.11.30]
560722  emp3b; epithelial membrane protein 3b (MAM blood group) precursor [KO:K26257]
561901  thbs1b; thrombospondin-1 isoform X1 [KO:K16857]
561963  bmp8a; bone morphogenetic protein 8A precursor [KO:K16622]
562072  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
562242  rps6kb1a; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
562822  bmpr2a; bone morphogenetic protein receptor type-2a precursor [KO:K04671] [EC:2.7.11.30]
563090  sin3aa; SIN3 transcription regulator family member Aa [KO:K11644]
563633  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
563884  tgfb1b; transforming growth factor beta-1 proprotein [KO:K13375]
564395  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
565091  si:dkey-5i3.5; uncharacterized protein LOC565091 [KO:K28359]
565612  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
566470  gdf6a; growth/differentiation factor 6-A precursor [KO:K20012]
566538  fstb; follistatin b isoform 1 precursor [KO:K04661]
566841  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
567111  crebbpb; CREB binding protein b [KO:K04498] [EC:2.3.1.48]
58092  smad3a; mothers against decapentaplegic homolog 3a [KO:K23605]
58145  bmpr1aa; bone morphogenetic protein receptor, type IAa precursor [KO:K04673] [EC:2.7.11.30]
64698  dcn; decorin precursor [KO:K04660]
664761  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
751630  zgc:153713; RhoA_like domain-containing protein [KO:K04513]
791822  fmoda; fibromodulin a precursor [KO:K08121]
792928  tgfbr1b; TGF-beta receptor type-1b precursor [KO:K04674] [EC:2.7.11.30]
794669  smad4b; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
794689  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X2 [KO:K04679]
795522  rbl1; retinoblastoma-like protein 1 [KO:K04681]
796607  emp3a; epithelial membrane protein 3 [KO:K26257]
797559  fmodb; fibromodulin [KO:K08121]
799352  ndr1; nodal-related 1 precursor [KO:K04666]
83496  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a precursor [KO:K10162]
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
Reference
PMID:38267638
  Authors
Wu M, Wu S, Chen W, Li YP
  Title
The roles and regulatory mechanisms of TGF-beta and BMP signaling in bone and cartilage development, homeostasis and disease.
  Journal
Cell Res 34:101-123 (2024)
DOI:10.1038/s41422-023-00918-9
Related
pathway
dre04010  MAPK signaling pathway
dre04110  Cell cycle
dre04120  Ubiquitin mediated proteolysis
dre04210  Apoptosis
KO pathway
ko04350   

DBGET integrated database retrieval system