KEGG   PATHWAY: els04350
Entry
els04350                    Pathway                                
Name
TGF-beta signaling pathway - Esox lucius (northern pike)
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
els04350  TGF-beta signaling pathway
els04350

Other DBs
GO: 0007179
Organism
Esox lucius (northern pike) [GN:els]
Gene
105015804  chrd; chordin isoform X2 [KO:K04657]
105006486  noggin-2-like [KO:K04658]
105031632  noggin-2 [KO:K04658]
105027560  noggin-3 [KO:K04658]
105022928  noggin-3-like [KO:K04658]
105009571  noggin [KO:K04658]
105017117  neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
105010551  gremlin-2-like [KO:K23318]
105015668  gremlin-1-like [KO:K23318]
105024321  grem1; gremlin-1 [KO:K23318]
105025290  grem2; gremlin-2 [KO:K23318]
105015675  thrombospondin-1-like [KO:K16857]
105024329  thrombospondin-1 [KO:K16857]
105020390  dcn; decorin [KO:K04660]
105007025  fibromodulin [KO:K08121]
105016920  fibromodulin [KO:K08121]
105016079  left-right determination factor 2-like [KO:K04668]
105028100  left-right determination factor 2 [KO:K04668]
105014942  follistatin-A-like [KO:K04661]
105014556  fst; follistatin isoform X1 [KO:K04661]
105017519  bmp2; bone morphogenetic protein 2 [KO:K21283]
105012052  bone morphogenetic protein 2 [KO:K21283]
109615754  bone morphogenetic protein 2 [KO:K21283]
105022886  bone morphogenetic protein 2 [KO:K21283]
105015523  bmp4; bone morphogenetic protein 4 [KO:K04662]
105019529  bmp6; bone morphogenetic protein 6 [KO:K16620]
105028312  inhibin beta B chain [KO:K22687]
105019970  inhibin beta B chain [KO:K22687]
105024677  inhbb; inhibin beta B chain [KO:K22687]
105018255  serotransferrin-2 [KO:K14736]
105021363  bmp5; bone morphogenetic protein 5 [KO:K04663]
105030895  bone morphogenetic protein 7 [KO:K16621]
105017334  bone morphogenetic protein 7-like [KO:K16621]
105007306  gdf5; growth/differentiation factor 5 [KO:K04664]
105007756  gdf6; growth/differentiation factor 6 [KO:K20012]
105030804  growth/differentiation factor 6-A [KO:K20012]
105009588  gdf7; growth/differentiation factor 7 [KO:K20013]
105011568  amh; muellerian-inhibiting factor [KO:K04665]
105017796  ifng1; interferon gamma 1 precursor [KO:K04687]
105031348  tumor necrosis factor-like [KO:K03156]
105007034  thrombospondin type-1 domain-containing protein 4 [KO:K23377]
105015393  thsd4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
105022664  fbn1; fibrillin-1 isoform X1 [KO:K06825]
105023261  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
105010856  transforming growth factor beta-1 proprotein [KO:K13375]
105027026  transforming growth factor beta-1 proprotein [KO:K13375]
105007294  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
105026733  transforming growth factor beta-2 proprotein [KO:K13376]
105015709  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
105029941  transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
105028288  inhibin beta A chain [KO:K04667]
105025163  inhibin beta A chain [KO:K04667]
105008963  nodal; nodal homolog [KO:K04666]
105015086  nodal homolog [KO:K04666]
105027013  nodal homolog 2-A-like [KO:K04666]
105010706  bmpr1a; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
105025159  bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
105014580  bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
105019986  activin receptor type-1-like isoform X1 [KO:K04675] [EC:2.7.11.30]
105022431  acvr1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
105007022  bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
105020079  bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
105022549  activin receptor type-2A isoform X3 [KO:K04670] [EC:2.7.11.30]
105016248  activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
105028484  hjv; hemojuvelin [KO:K23100]
105014007  neo1; neogenin isoform X1 [KO:K06766]
106023766  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
105021980  transferrin receptor protein 1 isoform X1 [KO:K06503]
105024999  tfrc; transferrin receptor protein 1 [KO:K06503]
105011541  repulsive guidance molecule A [KO:K23096]
105007008  rgmb; RGM domain family member B [KO:K06847]
105019479  TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
105024259  TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
105012782  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
105023521  tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
105030836  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
105017416  epithelial membrane protein 3-like [KO:K26257]
105013806  epithelial membrane protein 3-like [KO:K26257]
105028753  transforming growth factor beta activator LRRC32 isoform X2 [KO:K26316]
105026156  transforming growth factor beta activator LRRC32-like [KO:K26316]
105022608  nrros; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
105013550  activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
105017213  activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
105025736  acvr2b; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
105030502  activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
105022430  acvr1c; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
105019421  bambi; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
105007271  mothers against decapentaplegic homolog 1-like [KO:K04676]
105020940  mothers against decapentaplegic homolog 1 [KO:K04676]
105005996  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
105029976  smad9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
105014505  mothers against decapentaplegic homolog 2 [KO:K04500]
105005850  smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105013596  mothers against decapentaplegic homolog 3 [KO:K23605]
105031060  mothers against decapentaplegic homolog 4 [KO:K04501]
105014576  smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105025164  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105012677  mothers against decapentaplegic homolog 4-like isoform X1 [KO:K04501]
105013587  mothers against decapentaplegic homolog 6 [KO:K04677]
105031048  smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
105023527  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
105021636  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
105009663  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
105013159  E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
105006096  zinc finger FYVE domain-containing protein 16 isoform X3 [KO:K04679]
105031234  zfyve9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
105028158  zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
105025789  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105022041  cul1; cullin-1 [KO:K03347]
105024245  cullin-1 [KO:K03347]
105026694  skp1; S-phase kinase-associated protein 1 [KO:K03094]
105012809  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105006515  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105016855  rhoa; ras homolog family member A [KO:K04513]
105006799  rho-related GTP-binding protein RhoA-A [KO:K04513]
105026930  rho-related GTP-binding protein RhoA-C [KO:K04513]
105023679  rho-related GTP-binding protein RhoA-D [KO:K04513]
105025252  transforming protein RhoA [KO:K04513]
105019915  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
105011486  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
105025380  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105021738  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
105026079  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105026695  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105010995  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
105022224  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
105030187  rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
105027355  hamp; hepcidin [KO:K23106]
105027755  DNA-binding protein inhibitor ID-1-like [KO:K04680]
105017346  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
105026584  id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
105006541  DNA-binding protein inhibitor ID-3-A [KO:K17694]
105006451  rbl1; retinoblastoma-like protein 1 [KO:K04681]
105018215  transcription factor E2F4 [KO:K04682]
109614591  transcription factor E2F5-like [KO:K04682]
105016098  transcription factor E2F4 [KO:K04682]
105016568  transcription factor Dp-1 isoform X1 [KO:K04683]
105020059  tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
105012109  CREB-binding protein-like isoform X1 [KO:K04498] [EC:2.3.1.48]
105021653  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
105025802  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105025106  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
105031425  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
105022747  skil; ski-like protein [KO:K18499]
105023786  ski; ski oncogene [KO:K26503]
105028827  ski oncogene isoform X1 [KO:K26503]
105018683  sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
105014060  paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
105015808  probable histone deacetylase 1-B isoform X1 [KO:K06067] [EC:3.5.1.98]
105017885  hdac2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
105030237  probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
105027552  ncor1; nuclear receptor corepressor 1 isoform X3 [KO:K04650]
105027363  tgif1; homeobox protein TGIF1 isoform X2 [KO:K19383]
105016742  homeobox protein AKR-like [KO:K19553]
105019386  transcriptional regulator Myc [KO:K04377]
105029935  transcriptional regulator Myc-2 [KO:K04377]
105023685  myc; myc proto-oncogene protein [KO:K04377]
105021059  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
105027529  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
els04010  MAPK signaling pathway
els04110  Cell cycle
els04120  Ubiquitin mediated proteolysis
els04210  Apoptosis
KO pathway
ko04350   
LinkDB

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