KEGG   PATHWAY: gmu04350
Entry
gmu04350                    Pathway                                
Name
TGF-beta signaling pathway - Girardinichthys multiradiatus (darkedged splitfin)
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
gmu04350  TGF-beta signaling pathway
gmu04350

Other DBs
GO: 0007179
Organism
Girardinichthys multiradiatus (darkedged splitfin) [GN:gmu]
Gene
124855116  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
124855198  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
124855346  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
124855391  bmp4; bone morphogenetic protein 4 [KO:K04662]
124855579  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
124855701  [KO:K16857]
124855896  acvr1l; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
124855974  [KO:K06067] [EC:3.5.1.98]
124856135  gdf5; growth/differentiation factor 5 [KO:K04664]
124856311  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
124856374  nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
124856416  [KO:K22687]
124856436  [KO:K26257]
124856628  [KO:K19553]
124856857  si:dkey-5i3.5; transmembrane protein 53 [KO:K28359]
124856963  mych; myelocytomatosis oncogene homolog [KO:K04377]
124857154  [KO:K04513]
124857157  skib; v-ski avian sarcoma viral oncogene homolog b isoform X1 [KO:K26503]
124857159  [KO:K16621]
124857353  rbl1; retinoblastoma-like protein 1 [KO:K04681]
124857490  fmoda; fibromodulin a [KO:K08121]
124857569  sp1; transcription factor Sp1 isoform X1 [KO:K04684]
124857680  bmp6; bone morphogenetic protein 6 [KO:K16620]
124857712  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
124857980  [KO:K13596] [EC:2.7.11.30]
124857981  inhbaa; inhibin subunit beta Aa [KO:K04667]
124858107  tgfbr1b; TGF-beta receptor type-1b isoform X1 [KO:K04674] [EC:2.7.11.30]
124858143  [KO:K03347]
124858277  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a isoform X1 [KO:K10162]
124858340  tfr1b; transferrin receptor 1b [KO:K06503]
124858439  myca; transcriptional regulator Myc-A isoform X1 [KO:K04377]
124858529  tgif1; homeobox protein TGIF1 isoform X1 [KO:K19383]
124858641  bmp5; bone morphogenetic protein 5 [KO:K04663]
124858668  grem2a; gremlin-2 isoform X1 [KO:K23318]
124858735  bmpr1aa; bone morphogenetic protein receptor, type IAa [KO:K04673] [EC:2.7.11.30]
124858940  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
124859811  pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
124860378  smad5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
124860616  [KO:K04382] [EC:3.1.3.16]
124860655  [KO:K26316]
124860909  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
124861389  [KO:K04670] [EC:2.7.11.30]
124861473  [KO:K22687]
124861560  [KO:K04671] [EC:2.7.11.30]
124862304  [KO:K04658]
124862729  [KO:K04498] [EC:2.3.1.48]
124862821  [KO:K04498] [EC:2.3.1.48]
124863171  [KO:K03868] [EC:2.3.2.32]
124863178  [KO:K04678] [EC:2.3.2.26]
124863274  [KO:K04371] [EC:2.7.11.24]
124863406  [KO:K04678] [EC:2.3.2.26]
124863835  [KO:K04658]
124864197  [KO:K04498] [EC:2.3.1.48]
124864295  [KO:K04371] [EC:2.7.11.24]
124864508  [KO:K03868] [EC:2.3.2.32]
124864572  [KO:K04498] [EC:2.3.1.48]
124864596  [KO:K04678] [EC:2.3.2.26]
124864966  [KO:K04678] [EC:2.3.2.26]
124865538  [KO:K04501]
124865806  [KO:K04513]
124865817  [KO:K04513]
124865842  [KO:K23106]
124865873  gdf6a; growth/differentiation factor 6-A [KO:K20012]
124865875  tgfbr2b; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
124866019  [KO:K08121]
124866033  [KO:K23106]
124866078  hjv; hemojuvelin isoform X1 [KO:K23100]
124866331  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
124866577  [KO:K04677]
124866607  [KO:K04681]
124866620  [KO:K04682]
124866793  fbn1; fibrillin-1 [KO:K06825]
124866860  [KO:K11644]
124866892  [KO:K23377]
124867172  smad3a; mothers against decapentaplegic homolog 3a [KO:K23605]
124867188  neo1a; neogenin 1a [KO:K06766]
124867766  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
124867807  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
124867823  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
124868114  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
124868225  [KO:K04678] [EC:2.3.2.26]
124868300  [KO:K04688] [EC:2.7.11.1]
124869053  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
124869584  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
124869726  [KO:K04377]
124869806  skila; ski-like protein [KO:K18499]
124869863  [KO:K06503]
124869958  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
124870086  tmem53; transmembrane protein 53 [KO:K28359]
124870088  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
124870267  tfa; transferrin-a [KO:K14736]
124870275  [KO:K13596] [EC:2.7.11.30]
124870311  inhbab; inhibin subunit beta Ab [KO:K04667]
124870642  [KO:K21283]
124870836  [KO:K04513]
124870923  [KO:K13568] [EC:2.7.11.30]
124871055  [KO:K04675] [EC:2.7.11.30]
124871236  [KO:K04670] [EC:2.7.11.30]
124871452  [KO:K22687]
124871630  [KO:K04671] [EC:2.7.11.30]
124871723  tgfbr2l; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
124871969  tfdp1a; transcription factor Dp-1a [KO:K04683]
124872337  smad4a; mothers against decapentaplegic homolog 4a isoform X1 [KO:K04501]
124872478  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
124872660  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
124872950  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
124872974  [KO:K26257]
124872978  [KO:K04666]
124873081  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform X1 [KO:K13578] [EC:2.7.11.30]
124873439  zfyve9b; zinc finger FYVE domain-containing protein 9 [KO:K04679]
124873671  amh; muellerian-inhibiting factor isoform X1 [KO:K04665]
124873979  rgmd; RGM domain family, member D [KO:K23096]
124874616  ndr2; nodal-related 2 [KO:K04666]
124874824  nog2; noggin-2 [KO:K04658]
124874909  [KO:K20012]
124875315  nog3; noggin-3 [KO:K04658]
124875580  [KO:K21283]
124875764  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
124876187  lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
124876348  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
124876349  skp1; S-phase kinase-associated protein 1 [KO:K03094]
124876390  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
124876472  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
124876501  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
124877002  bmp7b; bone morphogenetic protein 7b [KO:K16621]
124877032  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
124877199  rgmb; RGM domain family member B [KO:K06847]
124877669  [KO:K04500]
124877743  [KO:K04382] [EC:3.1.3.16]
124877799  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124877955  bmpr1ba; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
124878113  [KO:K04501]
124878411  spaw; southpaw [KO:K04666]
124878481  fsta; follistatin-A [KO:K04661]
124879422  bmp8a; bone morphogenetic protein 8A isoform X1 [KO:K16622]
124879517  e2f4; transcription factor E2F4 [KO:K04682]
124879547  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
124879943  [KO:K04388] [EC:2.7.11.30]
124879956  tnfa; tumor necrosis factor a (TNF superfamily, member 2) isoform X1 [KO:K03156]
124880268  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
124880288  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
124881554  bmp2b; bone morphogenetic protein 2b [KO:K21283]
124881808  grem1a; gremlin-1a [KO:K23318]
124882113  [KO:K06067] [EC:3.5.1.98]
124882209  lft1; lefty1 [KO:K04668]
124882460  thbs1b; thrombospondin-1 isoform X1 [KO:K16857]
124882556  [KO:K13377]
124882755  [KO:K28359]
124882986  rgma; repulsive guidance molecule A [KO:K23096]
124883083  dcn; decorin [KO:K04660]
124883173  lemd3; inner nuclear membrane protein Man1 [KO:K19410]
124883543  chrd; chordin isoform X1 [KO:K04657]
124884239  rps6kb1b; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
124884249  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
124884668  bmp16; bone morphogenetic protein 16 [KO:K21283]
124884769  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
124884867  grem1b; gremlin-1 [KO:K23318]
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
gmu04010  MAPK signaling pathway
gmu04110  Cell cycle
gmu04120  Ubiquitin mediated proteolysis
gmu04210  Apoptosis
KO pathway
ko04350   

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