KEGG   PATHWAY: lcf04350
Entry
lcf04350                    Pathway                                
Name
TGF-beta signaling pathway - Lates calcarifer (barramundi perch)
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
lcf04350  TGF-beta signaling pathway
lcf04350

Other DBs
GO: 0007179
Organism
Lates calcarifer (barramundi perch) [GN:lcf]
Gene
108888190  chordin [KO:K04657]
108886807  LOW QUALITY PROTEIN: noggin-2 [KO:K04658]
108874440  noggin-like [KO:K04658]
108874729  nog3; noggin-3 [KO:K04658]
108875597  noggin-2-like [KO:K04658]
108886485  LOW QUALITY PROTEIN: neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
108887248  grem1a; gremlin-1a [KO:K23318]
108892418  grem1b; gremlin-1 [KO:K23318]
108897377  grem2a; gremlin-2 [KO:K23318]
108887258  LOW QUALITY PROTEIN: thrombospondin-1 [KO:K16857]
108892515  LOW QUALITY PROTEIN: thrombospondin-1-like [KO:K16857]
108889260  decorin [KO:K04660]
108889534  fmodb; fibromodulin [KO:K08121]
108889995  zgc:113307; lumican isoform X1 [KO:K08121]
108890011  LOW QUALITY PROTEIN: fibromodulin a [KO:K08121]
108895789  lefty1 [KO:K04668]
108881314  fsta; LOW QUALITY PROTEIN: follistatin-A [KO:K04661]
108896937  bmp2b; bone morphogenetic protein 2b [KO:K21283]
108889169  bone morphogenetic protein 2 [KO:K21283]
108900833  LOW QUALITY PROTEIN: bone morphogenetic protein 16 [KO:K21283]
108884186  anti-dorsalizing morphogenic protein [KO:K21283]
108875064  bone morphogenetic protein 4 [KO:K04662]
108883994  bone morphogenetic protein 6 isoform X1 [KO:K16620]
108884827  inhibin beta B chain [KO:K22687]
108887630  inhbb; inhibin beta B chain [KO:K22687]
108873208  LOW QUALITY PROTEIN: inhibin beta B chain-like [KO:K22687]
108883467  tfa; transferrin-a [KO:K14736]
108892399  bone morphogenetic protein 5 [KO:K04663]
108900181  bmp7b; bone morphogenetic protein 7b [KO:K16621]
108885678  LOW QUALITY PROTEIN: bone morphogenetic protein 7-like [KO:K16621]
108881926  bone morphogenetic protein 8A [KO:K16622]
108889735  LOW QUALITY PROTEIN: growth/differentiation factor 5 [KO:K04664]
108887645  gdf6a; growth/differentiation factor 6-A [KO:K20012]
108899057  gdf6b; LOW QUALITY PROTEIN: growth/differentiation factor 6-B [KO:K20012]
108877384  LOW QUALITY PROTEIN: muellerian-inhibiting factor [KO:K04665]
108896372  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
108899401  tnfb; tumor necrosis factor b (TNF superfamily, member 2) [KO:K03156]
108896464  thrombospondin type-1 domain-containing protein 4 [KO:K23377]
108897751  thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
108887902  fibrillin-1 [KO:K06825]
108895767  latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
108876160  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
108886089  transforming growth factor beta-2 proprotein [KO:K13376]
108872574  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
108895683  transforming growth factor beta-3 proprotein [KO:K13377]
108892510  transforming growth factor beta-3 proprotein [KO:K13377]
108884958  inhbab; inhibin subunit beta Ab [KO:K04667]
108891455  LOW QUALITY PROTEIN: inhibin beta A chain-like [KO:K04667]
108886046  LOW QUALITY PROTEIN: nodal homolog 2-A-like [KO:K04666]
108878075  southpaw [KO:K04666]
108899074  ndr2; nodal-related 2 [KO:K04666]
108895695  bmpr1aa; bone morphogenetic protein receptor, type IAa [KO:K04673] [EC:2.7.11.30]
108878299  bmpr1ba; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
108879878  bmpr1bb; bone morphogenetic protein receptor, type IBb [KO:K13578] [EC:2.7.11.30]
108901063  activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
108874998  acvr1l; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
108874243  bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
108880213  LOW QUALITY PROTEIN: bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
108888565  activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
108874503  acvr2aa; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
108873081  activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
108884728  LOW QUALITY PROTEIN: hemojuvelin [KO:K23100]
108887841  neo1a; neogenin 1a isoform X1 [KO:K06766]
108874236  transferrin receptor protein 2-like isoform X1 [KO:K23910]
108885109  tfr1b; transferrin receptor 1b [KO:K06503]
108883853  transferrin receptor protein 1 [KO:K06503]
108883855  transferrin receptor protein 1 [KO:K06503]
108875254  repulsive guidance molecule A [KO:K23096]
108877320  RGM domain family, member D [KO:K23096]
108878320  RGM domain family member B [KO:K06847]
108898453  LOW QUALITY PROTEIN: TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
108889085  TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
108881978  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
108876301  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
108899899  emp3a; epithelial membrane protein 3 [KO:K26257]
108891696  epithelial membrane protein 3 [KO:K26257]
108893873  transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
108882872  transforming growth factor beta activator LRRC32 [KO:K26316]
108898247  transforming growth factor beta activator LRRC33 [KO:K26317]
108876546  LOW QUALITY PROTEIN: activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
108881466  activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
108884221  activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
108891453  acvr2ba; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
108901072  activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
108898273  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
108893108  mothers against decapentaplegic homolog 1 [KO:K04676]
108878855  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
108893720  mothers against decapentaplegic homolog 9 [KO:K16791]
108878489  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
108886506  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
108887878  smad3a; mothers against decapentaplegic homolog 3 [KO:K23605]
108888967  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
108878621  mothers against decapentaplegic homolog 4 [KO:K04501]
108884647  mothers against decapentaplegic homolog 4 [KO:K04501]
108896340  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
108887879  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 6-like [KO:K04677]
108886465  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
108874091  mothers against decapentaplegic homolog 7 [KO:K19631]
108877640  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
108898653  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
108875765  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
108877407  zfyve9b; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
108897682  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
108884256  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
108877581  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
108885000  cullin-1 [KO:K03347]
108893670  S-phase kinase-associated protein 1 [KO:K03094]
108881026  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108891348  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108877880  rho-related GTP-binding protein RhoA-C [KO:K04513]
108900458  rho-related GTP-binding protein RhoA-C [KO:K04513]
108886517  transforming protein RhoA [KO:K04513]
108882564  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
108876465  rho-related GTP-binding protein RhoA-D isoform X1 [KO:K04513]
108883337  rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
108895267  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
108893912  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
108882943  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
108875225  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
108900110  ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
108893900  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
108901179  ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
108873771  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
108887803  hepcidin-like [KO:K23106]
108887813  hepcidin-like isoform X3 [KO:K23106]
108887824  hepcidin-like [KO:K23106]
108899523  hepcidin-1 [KO:K23106]
108885609  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
108888143  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
108875025  DNA-binding protein inhibitor ID-3 [KO:K17694]
108876325  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
108901481  LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
108877790  transcription factor E2F4 [KO:K04682]
108901918  LOW QUALITY PROTEIN: transcription factor E2F4 [KO:K04682]
108884147  e2f5; transcription factor E2F5 [KO:K04682]
108901058  tfdp1a; transcription factor Dp-1a [KO:K04683]
108877577  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108889106  LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
108886160  crebbpb; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108885407  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108884839  transcription factor Sp1 isoform X1 [KO:K04684]
108884149  skila; ski-like protein isoform X1 [KO:K18499]
108900527  LOW QUALITY PROTEIN: v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
108899258  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
108883028  sin3aa; LOW QUALITY PROTEIN: SIN3 transcription regulator family member Aa [KO:K11644]
108887830  paired amphipathic helix protein Sin3a [KO:K11644]
108900358  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
108899297  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
108893218  nuclear receptor corepressor 1 isoform X1 [KO:K04650]
108896283  tgif1; homeobox protein TGIF1 [KO:K19383]
108884033  uncharacterized protein LOC108884033 [KO:K19553]
108895017  LOW QUALITY PROTEIN: transcriptional regulator Myc-A [KO:K04377]
108882464  transcriptional regulator Myc-B [KO:K04377]
108874403  mych; myelocytomatosis oncogene homolog [KO:K04377]
108896541  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
108885170  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
lcf04010  MAPK signaling pathway
lcf04110  Cell cycle
lcf04120  Ubiquitin mediated proteolysis
lcf04210  Apoptosis
KO pathway
ko04350   
LinkDB

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