KEGG   PATHWAY: psex04350
Entry
psex04350                   Pathway                                
Name
TGF-beta signaling pathway - Polypterus senegalus (gray bichir)
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
psex04350  TGF-beta signaling pathway
psex04350

Other DBs
GO: 0007179
Organism
Polypterus senegalus (gray bichir) [GN:psex]
Gene
120514495  rbl1; retinoblastoma-like protein 1 [KO:K04681]
120514604  id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
120515073  bmp7b; bone morphogenetic protein 7b [KO:K16621]
120515160  tmem53; transmembrane protein 53 [KO:K28359]
120515187  gdf5; growth/differentiation factor 5 [KO:K04664]
120515765  tgfbr2b; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
120515939  gdf6a; growth/differentiation factor 6-A [KO:K20012]
120516313  bmp5; bone morphogenetic protein 5 [KO:K04663]
120516446  ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
120516503  bmp2a; bone morphogenetic protein 2 isoform X1 [KO:K21283]
120516809  grem2b; gremlin-2b [KO:K23318]
120517306  [KO:K06067] [EC:3.5.1.98]
120517425  [KO:K04658]
120517831  id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
120517855  bmp8a; bone morphogenetic protein 8A [KO:K16622]
120518032  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
120518451  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
120518644  [KO:K26257]
120518861  bmp4; bone morphogenetic protein 4 [KO:K04662]
120518878  [KO:K23318]
120518968  thbs1b; thrombospondin-1 [KO:K16857]
120519079  ndr2; nodal-related 2 [KO:K04666]
120519125  [KO:K21283]
120519336  smad6b; mothers against decapentaplegic homolog 6b [KO:K04677]
120523386  tfdp1b; transcription factor Dp-1b isoform X1 [KO:K04683]
120523810  lrrc32; transforming growth factor beta activator LRRC32 [KO:K26316]
120524011  smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
120524804  [KO:K22687]
120524835  acvr1ba; activin A receptor type 1Ba [KO:K13567] [EC:2.7.11.30]
120524944  [KO:K04684]
120525110  tfr2; transferrin receptor protein 2 isoform X1 [KO:K23910]
120525195  [KO:K04513]
120525557  [KO:K06067] [EC:3.5.1.98]
120525682  [KO:K04513]
120525684  [KO:K20013]
120526029  [KO:K17693]
120526163  fmoda; fibromodulin a [KO:K08121]
120526626  lft1; lefty1 [KO:K04668]
120527116  smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
120527232  smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
120527544  bmpr1ba; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
120528731  hjv; hemojuvelin [KO:K23100]
120529478  cul1b; cullin-1b [KO:K03347]
120529526  [KO:K04667]
120529587  tgfbr1b; TGF-beta receptor type-1b [KO:K04674] [EC:2.7.11.30]
120529658  acvr2ba; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
120529758  bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a [KO:K10162]
120529802  [KO:K04377]
120529842  bmp6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
120530131  e2f5; transcription factor E2F5 isoform X1 [KO:K04682]
120530313  rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
120530370  tgif1; homeobox protein TGIF1 [KO:K19383]
120530737  [KO:K22687]
120530780  tgfbr2l; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
120531037  nbl1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
120531054  skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503]
120531529  [KO:K04688] [EC:2.7.11.1]
120531551  ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
120531704  [KO:K04670] [EC:2.7.11.30]
120531752  [KO:K13568] [EC:2.7.11.30]
120531753  [KO:K04675] [EC:2.7.11.30]
120531931  [KO:K04671] [EC:2.7.11.30]
120532326  adamtsl7; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
120532398  rgmb; RGM domain family member B [KO:K06847]
120532483  fsta; follistatin-A isoform X1 [KO:K04661]
120532622  ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120532830  zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
120533041  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120533046  smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
120533098  pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
120533992  [KO:K18499]
120534131  si:dkey-5i3.5; uncharacterized protein si:dkey-5i3.5 [KO:K28359]
120534309  dcn; decorin [KO:K04660]
120534730  nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
120535399  [KO:K04677]
120535403  e2f4; transcription factor E2F4 [KO:K04682]
120535843  [KO:K03456]
120535935  tfa; transferrin-a [KO:K14736]
120536086  [KO:K06503]
120536571  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120536701  chrd; chordin [KO:K04657]
120536924  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120536925  ep300b; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
120537437  [KO:K26316]
120537693  rgmd; RGM domain family, member D [KO:K23096]
120538075  [KO:K04688] [EC:2.7.11.1]
120538179  smad10a; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
120538398  [KO:K19553]
120538679  bmp16; bone morphogenetic protein 16 [KO:K21283]
120538772  [KO:K13375]
120538882  [KO:K04673] [EC:2.7.11.30]
120539363  tgfb5; transforming growth factor beta-2 proprotein [KO:K13376]
120539556  lemd3; inner nuclear membrane protein Man1 [KO:K19410]
120539751  [KO:K04666]
120540086  [KO:K03456]
120540092  [KO:K23106]
120540437  [KO:K04513]
120540544  fbn1; fibrillin-1 [KO:K06825]
120540631  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120541448  [KO:K06766]
120541552  rgma; repulsive guidance molecule A [KO:K23096]
120541663  smad3b; mothers against decapentaplegic homolog 3b isoform X1 [KO:K23605]
120541684  sin3aa; SIN3 transcription regulator family member Aa isoform X1 [KO:K11644]
120541898  [KO:K04498] [EC:2.3.1.48]
120542003  ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120542020  smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
120542076  skp1; S-phase kinase-associated protein 1 [KO:K03094]
120542869  nog2; noggin-2 [KO:K04658]
120543183  rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513]
120543200  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
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
psex04010  MAPK signaling pathway
psex04110  Cell cycle
psex04120  Ubiquitin mediated proteolysis
psex04210  Apoptosis
KO pathway
ko04350   

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