KEGG   PATHWAY: msam04350
Entry
msam04350                   Pathway                                
Name
TGF-beta signaling pathway - Micropterus salmoides (largemouth bass)
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
msam04350  TGF-beta signaling pathway
msam04350

Other DBs
GO: 0007179
Organism
Micropterus salmoides (largemouth bass) [GN:msam]
Gene
119881913  [KO:K23100]
119882023  mych; myelocytomatosis oncogene homolog [KO:K04377]
119882035  [KO:K04683]
119882172  [KO:K04660]
119882263  chrd; chordin isoform X1 [KO:K04657]
119882311  ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
119882554  rps6kb1b; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
119882881  tgfb1a; transforming growth factor, beta 1a [KO:K13375]
119883176  bmp16; bone morphogenetic protein 16 [KO:K21283]
119883833  [KO:K04678] [EC:2.3.2.26]
119884920  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
119884942  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
119885091  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
119885515  [KO:K16621]
119885543  [KO:K04513]
119885655  si:dkey-264d12.4; epithelial membrane protein 3 [KO:K26257]
119885701  [KO:K13567] [EC:2.7.11.30]
119885812  sp1; transcription factor Sp1 [KO:K04684]
119885930  [KO:K22687]
119886227  nbl1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
119886229  [KO:K04513]
119886258  rbl1; retinoblastoma-like protein 1 [KO:K04681]
119886325  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119886367  skib; v-ski avian sarcoma viral oncogene homolog b isoform X1 [KO:K26503]
119886542  fmoda; fibromodulin a [KO:K08121]
119886563  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
119886677  gdf5; growth/differentiation factor 5 [KO:K04664]
119886890  zgc:113307; lumican isoform X1 [KO:K08121]
119886945  [KO:K19553]
119887120  [KO:K06503]
119887503  [KO:K04666]
119887885  [KO:K04501]
119888380  [KO:K26316]
119888841  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
119888909  [KO:K04382] [EC:3.1.3.16]
119889077  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
119889343  pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
119889798  crebbpb; CREB binding protein b isoform X1 [KO:K04498] [EC:2.3.1.48]
119889827  neo1a; neogenin 1a isoform X1 [KO:K06766]
119889934  [KO:K11644]
119890083  smad3a; mothers against decapentaplegic homolog 3a [KO:K23605]
119890105  [KO:K04682]
119890205  fbn1; LOW QUALITY PROTEIN: fibrillin-1 [KO:K06825]
119890561  [KO:K04677]
119890788  [KO:K23377]
119891295  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119891347  bmpr1ba; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
119891427  [KO:K04501]
119891592  [KO:K04382] [EC:3.1.3.16]
119891755  [KO:K04500]
119891900  spaw; southpaw [KO:K04666]
119892235  rgmb; RGM domain family member B [KO:K06847]
119892396  fsta; follistatin-A isoform X1 [KO:K04661]
119893246  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
119893348  rgma; repulsive guidance molecule A [KO:K23096]
119893375  smad3b; mothers against decapentaplegic homolog 3b [KO:K23605]
119893941  e2f4; transcription factor E2F4 isoform X1 [KO:K04682]
119893958  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
119894737  [KO:K04658]
119895177  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
119895296  ncor1; LOW QUALITY PROTEIN: nuclear receptor corepressor 1 [KO:K04650]
119895400  rps6kb1a; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119895465  lrrc32; transforming growth factor beta activator LRRC32 [KO:K26316]
119895680  skp1; S-phase kinase-associated protein 1 [KO:K03094]
119895758  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119896622  [KO:K03347]
119896887  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
119897052  inhbaa; inhibin subunit beta Aa [KO:K04667]
119897144  [KO:K03156]
119897237  [KO:K23106]
119897268  [KO:K13596] [EC:2.7.11.30]
119897995  [KO:K23106]
119897996  [KO:K23106]
119897997  [KO:K23106]
119897998  [KO:K23106]
119898009  gdf6a; growth/differentiation factor 6-A [KO:K20012]
119898089  id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
119898112  tgfbr2b; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
119898229  [KO:K23100]
119898232  [KO:K04501]
119898485  [KO:K04658]
119898861  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
119898939  cdkn2a/b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
119899092  [KO:K23377]
119899331  [KO:K04678] [EC:2.3.2.26]
119899431  crebbpa; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
119899805  [KO:K04688] [EC:2.7.11.1]
119900820  zfyve9b; zinc finger FYVE domain-containing protein 9 [KO:K04679]
119900870  amh; muellerian-inhibiting factor [KO:K04665]
119900898  rgmd; RGM domain family, member D [KO:K23096]
119901066  bmpr2b; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
119901828  [KO:K13596] [EC:2.7.11.30]
119901877  skila; ski-like protein isoform X1 [KO:K18499]
119901889  e2f5; transcription factor E2F5 [KO:K04682]
119901969  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
119902102  tfa; transferrin-a [KO:K14736]
119902413  tfr1a; transferrin receptor 1a [KO:K06503]
119902666  [KO:K04377]
119902753  inhbab; inhibin subunit beta Ab [KO:K04667]
119902840  zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
119903030  [KO:K21283]
119903469  inhbb; inhibin beta B chain [KO:K22687]
119903610  [KO:K04671] [EC:2.7.11.30]
119903741  acvr2aa; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
119903766  tgfbr2l; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
119904031  [KO:K13568] [EC:2.7.11.30]
119904033  [KO:K04675] [EC:2.7.11.30]
119904272  tfdp1a; transcription factor Dp-1a [KO:K04683]
119904984  [KO:K04513]
119905275  acvr2ab; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
119905306  bmp7b; bone morphogenetic protein 7b isoform X1 [KO:K16621]
119905430  [KO:K04513]
119905633  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
119905639  [KO:K26257]
119905729  rhoab; rho-related GTP-binding protein RhoA-B [KO:K04513]
119905834  tgfbr1b; TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
119905991  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
119906160  fmodb; fibromodulin [KO:K08121]
119906549  [KO:K23377]
119906559  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
119906688  tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156]
119906712  gdf6b; growth/differentiation factor 6-B [KO:K20012]
119906838  bmp8a; bone morphogenetic protein 8A [KO:K16622]
119907112  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
119907183  [KO:K06067] [EC:3.5.1.98]
119907257  [KO:K04388] [EC:2.7.11.30]
119907298  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
119907990  bmp6; bone morphogenetic protein 6 [KO:K16620]
119908480  lft1; lefty1 [KO:K04668]
119908523  bmp2b; bone morphogenetic protein 2b [KO:K21283]
119909012  thbs1b; thrombospondin-1 [KO:K16857]
119909029  [KO:K06067] [EC:3.5.1.98]
119909065  [KO:K22687]
119909133  [KO:K13377]
119909287  grem1a; gremlin-1a [KO:K23318]
119910104  [KO:K06067] [EC:3.5.1.98]
119910151  [KO:K16857]
119910153  grem1b; gremlin-1 [KO:K23318]
119910175  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
119910406  bmp4; bone morphogenetic protein 4 [KO:K04662]
119910505  id2a; DNA-binding protein inhibitor ID-2a [KO:K17693]
119910627  acvr1l; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
119910678  tgif1; homeobox protein TGIF1 [KO:K19383]
119910740  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
119911452  [KO:K04673] [EC:2.7.11.30]
119911475  myca; transcriptional regulator Myc-A [KO:K04377]
119912409  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
119912484  tfr1b; LOW QUALITY PROTEIN: transferrin receptor 1b [KO:K06503]
119914039  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
119914293  bmpr1bb; bone morphogenetic protein receptor, type IBb isoform X1 [KO:K13578] [EC:2.7.11.30]
119914314  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
119914319  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
119914352  smad4a; mothers against decapentaplegic homolog 4a [KO:K04501]
119914826  [KO:K04666]
119916133  [KO:K21283]
119916335  nog2; noggin-2 [KO:K04658]
119916502  nog3; noggin-3 [KO:K04658]
119916588  ep300a; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
119917025  bmp5; bone morphogenetic protein 5 [KO:K04663]
119917373  ltbp1; LOW QUALITY PROTEIN: latent-transforming growth factor beta-binding protein 1 [KO:K19559]
119917429  grem2a; gremlin-2 [KO:K23318]
119918080  dcn; decorin [KO:K04660]
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
msam04010  MAPK signaling pathway
msam04110  Cell cycle
msam04120  Ubiquitin mediated proteolysis
msam04210  Apoptosis
KO pathway
ko04350   

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