KEGG   PATHWAY: oaa04350
Entry
oaa04350                    Pathway                                
Name
TGF-beta signaling pathway - Ornithorhynchus anatinus (platypus)
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
oaa04350  TGF-beta signaling pathway
oaa04350

Other DBs
GO: 0007179
Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
100073519  RHOA; transforming protein RhoA isoform X2 [KO:K04513]
100073945  CUL1; cullin-1 [KO:K03347]
100074293  RGMA; repulsive guidance molecule A [KO:K23096]
100074840  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
100075172  PITX2; pituitary homeobox 2 [KO:K04686]
100075296  E2F4; LOW QUALITY PROTEIN: transcription factor E2F4 [KO:K04682]
100075412  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100075415  INHBA; inhibin beta A chain [KO:K04667]
100075653  TF; serotransferrin [KO:K14736]
100075750  FST; follistatin isoform X1 [KO:K04661]
100075865  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
100076606  NEO1; neogenin isoform X1 [KO:K06766]
100076684  NCOR1; nuclear receptor corepressor 1 isoform X3 [KO:K04650]
100076928  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100076960  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100076965  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100077006  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
100077136  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100077247  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
100077258  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
100077376  TGIF2; homeobox protein TGIF2 [KO:K19553]
100077505  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
100077843  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100078158  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
100078398  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
100078497  FBN1; LOW QUALITY PROTEIN: fibrillin-1 [KO:K06825]
100078756  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
100078852  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100079193  [KO:K04513]
100079347  BMP7; bone morphogenetic protein 7 [KO:K16621]
100079391  MYC; myc proto-oncogene protein [KO:K04377]
100079648  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
100079802  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
100079987  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
100079988  DCN; decorin [KO:K04660]
100080090  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
100080176  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
100080510  [KO:K04498] [EC:2.3.1.48]
100080533  GDF7; growth/differentiation factor 7 [KO:K20013]
100081304  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
100081555  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100081575  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
100082000  [KO:K04668]
100082155  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100082390  RGMB; LOW QUALITY PROTEIN: RGM domain family member B [KO:K06847]
100082571  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
100082697  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100082731  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100083679  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100083684  BMP6; bone morphogenetic protein 6 [KO:K16620]
100083836  GREM2; gremlin-2 [KO:K23318]
100084030  BMP2; bone morphogenetic protein 2 [KO:K21283]
100084227  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100084266  [KO:K21283]
100084835  HJV; hemojuvelin [KO:K23100]
100085252  [KO:K16622]
100085267  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
100085480  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100085643  TNF; tumor necrosis factor [KO:K03156]
100085963  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
100086043  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
100086120  SKI; ski oncogene [KO:K26503]
100086343  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
100086400  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
100086487  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100086559  TFRC; transferrin receptor protein 1 [KO:K06503]
100086574  BMPR1B; bone morphogenetic protein receptor type-1B isoform X2 [KO:K13578] [EC:2.7.11.30]
100086592  GDF6; growth/differentiation factor 6 [KO:K20012]
100087780  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100088266  E2F5; transcription factor E2F5 [KO:K04682]
100088815  NODAL; nodal homolog [KO:K04666]
100089255  BMP4; bone morphogenetic protein 4 [KO:K04662]
100089467  CHRD; chordin isoform X1 [KO:K04657]
100089503  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
100089842  FMOD; fibromodulin [KO:K08121]
100089852  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
100090340  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100090625  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
100090790  GREM1; gremlin-1 [KO:K23318]
100090807  SKIL; ski-like protein [KO:K18499]
100091678  [KO:K23096]
100092358  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
100092988  THBS1; thrombospondin-1 [KO:K16857]
100093591  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100681929  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
103164998  [KO:K26168]
103165788  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
103167286  INHBC; inhibin beta C chain [KO:K22688]
103168191  ZFYVE9; LOW QUALITY PROTEIN: zinc finger FYVE domain-containing protein 9 [KO:K04679]
107548055  [KO:K04668]
114806015  GDF5; growth/differentiation factor 5 [KO:K04664]
114806127  [KO:K04658]
114806170  RBL1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
114807456  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
114807863  [KO:K04685]
114808649  [KO:K16790]
114808765  AMH; muellerian-inhibiting factor [KO:K04665]
114810112  [KO:K21283]
114811187  INHBB; inhibin beta B chain [KO:K22687]
114811983  [KO:K19558]
114812005  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
114812134  [KO:K23106]
114814570  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
114814573  [KO:K22689]
114814678  EMP3; epithelial membrane protein 3 [KO:K26257]
114814764  SP1; transcription factor Sp1 [KO:K04684]
114816908  NOG; noggin [KO:K04658]
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
oaa04010  MAPK signaling pathway
oaa04110  Cell cycle
oaa04120  Ubiquitin mediated proteolysis
oaa04210  Apoptosis
KO pathway
ko04350   

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