KEGG   PATHWAY: ely04350
Entry
ely04350                    Pathway                                
Name
TGF-beta signaling pathway - Epinephelus lanceolatus (giant grouper)
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
ely04350  TGF-beta signaling pathway
ely04350

Other DBs
GO: 0007179
Organism
Epinephelus lanceolatus (giant grouper) [GN:ely]
Gene
117259339  chrd; chordin [KO:K04657]
117268823  noggin-like [KO:K04658]
117246894  nog2; noggin-2 [KO:K04658]
117247444  nog3; noggin-3 [KO:K04658]
117256612  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
117270343  grem1a; gremlin-1a [KO:K23318]
117247860  gremlin-2-like [KO:K23318]
117248236  gremlin-2-like [KO:K23318]
117266902  grem1b; gremlin-1 [KO:K23318]
117270742  thbs1b; thrombospondin-1 [KO:K16857]
117267199  thrombospondin-1-like [KO:K16857]
117249419  dcn; decorin [KO:K04660]
117256574  zgc:113307; lumican isoform X1 [KO:K08121]
117256486  fmoda; fibromodulin a isoform X1 [KO:K08121]
117258520  fmodb; fibromodulin [KO:K08121]
117271304  lft1; lefty1 [KO:K04668]
117253215  fsta; follistatin-A isoform X1 [KO:K04661]
117270466  bmp2b; bone morphogenetic protein 2b [KO:K21283]
117271446  admp; anti-dorsalizing morphogenic protein [KO:K21283]
117247730  bone morphogenetic protein 2-like [KO:K21283]
117260320  bmp16; bone morphogenetic protein 16 [KO:K21283]
117266620  bmp4; bone morphogenetic protein 4 [KO:K04662]
117264854  bmp6; bone morphogenetic protein 6 [KO:K16620]
117250114  inhibin beta B chain-like [KO:K22687]
117256529  inhibin beta B chain [KO:K22687]
117251812  inhbb; inhibin beta B chain [KO:K22687]
117263649  tfa; transferrin-a [KO:K14736]
117247906  bmp5; bone morphogenetic protein 5 [KO:K04663]
117257304  bone morphogenetic protein 7-like [KO:K16621]
117258068  bone morphogenetic protein 7-like [KO:K16621]
117263993  bmp8a; bone morphogenetic protein 8A [KO:K16622]
117256613  gdf5; growth/differentiation factor 5 [KO:K04664]
117263281  gdf6b; growth/differentiation factor 6-B [KO:K20012]
117265455  gdf6a; growth/differentiation factor 6-A [KO:K20012]
117254246  amh; muellerian-inhibiting factor [KO:K04665]
117265588  tnfb; tumor necrosis factor b (TNF superfamily, member 2) [KO:K03156]
117263947  tumor necrosis factor-like [KO:K03156]
117247288  thrombospondin type-1 domain-containing protein 4-like isoform X1 [KO:K23377]
117255137  adamtsl7; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
117264531  fbn1; fibrillin-1 [KO:K06825]
117248146  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
117259934  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
117251444  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
117264719  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
117270870  transforming growth factor beta-3 proprotein-like [KO:K13377]
117267019  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
117264506  inhbaa; inhibin subunit beta Aa [KO:K04667]
117272343  inhbab; inhibin subunit beta Ab [KO:K04667]
117250581  nodal homolog [KO:K04666]
117252026  spaw; LOW QUALITY PROTEIN: southpaw [KO:K04666]
117270229  ndr1; nodal-related 1 [KO:K04666]
117247641  ndr2; nodal-related 2 [KO:K04666]
117248329  bone morphogenetic protein receptor type-1A-like isoform X1 [KO:K04673] [EC:2.7.11.30]
117269956  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform X1 [KO:K13578] [EC:2.7.11.30]
117253034  bmpr1ba; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
117251361  activin receptor type-1-like [KO:K04675] [EC:2.7.11.30]
117266999  acvr1l; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
117249830  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
117251488  bone morphogenetic protein receptor type-2-like [KO:K04671] [EC:2.7.11.30]
117250046  activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
117251307  acvr2aa; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
117266134  hjv; hemojuvelin [KO:K23100]
117253814  neo1a; neogenin 1a isoform X1 [KO:K06766]
117272727  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
117264423  tfr1b; transferrin receptor 1b [KO:K06503]
117271418  tfr1a; transferrin receptor 1a [KO:K06503]
117262669  rgma; repulsive guidance molecule A [KO:K23096]
117254456  rgmd; RGM domain family, member D [KO:K23096]
117253050  rgmb; RGM domain family member B [KO:K06847]
117264981  tgfbr1b; TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
117251018  tgfbr2l; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
117264185  TGF-beta receptor type-2-like isoform X1 [KO:K04388] [EC:2.7.11.30]
117266445  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
117257107  epithelial membrane protein 3-like [KO:K26257]
117258714  epithelial membrane protein 3-like [KO:K26257]
117270861  lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
117260675  transforming growth factor beta activator LRRC32-like isoform X1 [KO:K26316]
117264458  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
117257141  activin receptor type-1B-like [KO:K13567] [EC:2.7.11.30]
117258425  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
117264878  activin receptor type-2B-like [KO:K13596] [EC:2.7.11.30]
117271968  activin receptor type-2B-like [KO:K13596] [EC:2.7.11.30]
117249679  activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
117264384  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
117256027  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
117261251  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
117271266  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
117252759  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
117262313  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
117258017  mothers against decapentaplegic homolog 3 [KO:K23605]
117263121  si:dkey-222b8.1; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
117270121  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
117252732  mothers against decapentaplegic homolog 4-like [KO:K04501]
117262251  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
117252100  mothers against decapentaplegic homolog 6-like [KO:K04677]
117269656  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
117255527  E3 ubiquitin-protein ligase SMURF2-like [KO:K04678] [EC:2.3.2.26]
117268066  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
117268230  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
117269529  zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
117253402  zfyve9b; zinc finger FYVE domain-containing protein 9 [KO:K04679]
117272436  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
117268068  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
117264677  cullin-1 [KO:K03347]
117262658  skp1; S-phase kinase-associated protein 1 [KO:K03094]
117268290  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
117253153  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117256806  rhoca; ras homolog family member Ca [KO:K04513]
117257391  transforming protein RhoA [KO:K04513]
117257918  rho-related GTP-binding protein RhoA-D [KO:K04513]
117258243  rho-related GTP-binding protein RhoA-C-like [KO:K04513]
117258264  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
117258873  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
117272237  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
117259927  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
117252712  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
117271769  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
117260490  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
117259591  ribosomal protein S6 kinase beta-1-like [KO:K04688] [EC:2.7.11.1]
117255533  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
117268077  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
117265527  hamp; hepcidin-1 [KO:K23106]
117266106  hepcidin-like [KO:K23106]
117266107  hepcidin-like isoform X1 [KO:K23106]
117266108  hepcidin-like [KO:K23106]
117266296  hepcidin-like [KO:K23106]
117256532  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
117267501  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
117266738  DNA-binding protein inhibitor ID-3-A-like [KO:K17694]
117266743  DNA-binding protein inhibitor ID-3-A-like [KO:K17694]
117266503  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
117251192  retinoblastoma-like protein 2 [KO:K04681]
117257401  rbl1; retinoblastoma-like protein 1 [KO:K04681]
117252439  retinoblastoma-like protein 2 isoform X1 [KO:K04681]
117262698  e2f4; transcription factor E2F4 [KO:K04682]
117251317  transcription factor E2F4-like [KO:K04682]
117271737  transcription factor E2F5-like isoform X1 [KO:K04682]
117248446  transcription factor Dp-1-like [KO:K04683]
117268829  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117246714  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117255129  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117267836  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
117256362  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
117271879  skila; ski-like protein isoform X1 [KO:K18499]
117258172  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
117256752  skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503]
117262160  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
117253130  paired amphipathic helix protein Sin3a-like [KO:K11644]
117262997  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
117270371  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
117267413  histone deacetylase 1-like isoform X1 [KO:K06067] [EC:3.5.1.98]
117264003  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
117264760  tgif1; homeobox protein TGIF1 [KO:K19383]
117257284  mych; myelocytomatosis oncogene homolog [KO:K04377]
117264404  myca; transcriptional regulator Myc-A [KO:K04377]
117271564  transcriptional regulator Myc-B-like [KO:K04377]
117260522  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
ely04010  MAPK signaling pathway
ely04110  Cell cycle
ely04120  Ubiquitin mediated proteolysis
ely04210  Apoptosis
KO pathway
ko04350   
LinkDB

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