KEGG   PATHWAY: xla04350
Entry
xla04350                    Pathway                                
Name
TGF-beta signaling pathway - Xenopus laevis (African clawed frog)
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
xla04350  TGF-beta signaling pathway
xla04350

Other DBs
GO: 0007179
Organism
Xenopus laevis (African clawed frog) [GN:xla]
Gene
100036830  admp2.L; antidorsalizing morphogenetic protein 2 L homeolog precursor [KO:K21283]
100037050  smad6.S; uncharacterized protein LOC100037050 [KO:K04677]
100137625  tnf.L; tumor necrosis factor L homeolog [KO:K03156]
100158336  nrros.S; negative regulator of reactive oxygen species S homeolog precursor [KO:K26317]
100337509  id4.L; inhibitor of DNA binding 4, HLH protein L homeolog [KO:K17695]
100337601  smad9.L; SMAD family member 9 L homeolog [KO:K16791]
100381051  neo1.L; neogenin isoform X1 [KO:K06766]
101027283  ifng.L; interferon gamma [KO:K04687]
108695261  rock1.S; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
108695369  e2f5.S; transcription factor E2F5 [KO:K04682]
108696828  hamp2.L; hepcidin [KO:K23106]
108696829  [KO:K23106]
108697489  nodal.S; nodal homolog 4-B [KO:K04666]
108697874  nbl1.S; neuroblastoma suppressor of tumorigenicity 1-like [KO:K19558]
108698893  lrrc32.2.L; transforming growth factor beta activator LRRC32 [KO:K26316]
108699361  hjv.L; hemojuvelin [KO:K23100]
108699473  smad6.2.L; mothers against decapentaplegic homolog 6 [KO:K04677]
108700235  tnf.S; tumor necrosis factor [KO:K03156]
108700276  tgfb1.S; transforming growth factor beta-1 proprotein-like [KO:K13375]
108700348  hjv.S; hemojuvelin [KO:K23100]
108700426  smad4.2.S; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
108701209  [KO:K04678] [EC:2.3.2.26]
108701335  acvr1c.L; activin receptor type-1C-like [KO:K13568] [EC:2.7.11.30]
108701455  bmpr2.L; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
108702362  gdf5.S; growth/differentiation factor 5 [KO:K04664]
108702613  bmp7.1.S; bone morphogenetic protein 7 [KO:K16621]
108702771  rbl1.S; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
108702885  tgfbr2l.S; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
108702893  inhbb.S; inhibin beta B chain [KO:K22687]
108702964  acvr1c.S; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
108703087  smurf1.S; E3 ubiquitin-protein ligase SMURF1-like isoform X1 [KO:K04678] [EC:2.3.2.26]
108703173  nog2.S; noggin-2 [KO:K04658]
108703982  [KO:K16791]
108704141  nog.S; noggin-like [KO:K04658]
108705373  skil.S; ski-like protein isoform X2 [KO:K18499]
108705601  [KO:K23106]
108706748  bmpr1b.S; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
108706827  [KO:K04382] [EC:3.1.3.16]
108706872  amh.S; muellerian-inhibiting factor [KO:K04665]
108706939  cdkn2b.S; cyclin-dependent kinase inhibitor 2A [KO:K04685]
108707225  rgmb.S; RGM domain family member B [KO:K06847]
108707248  zfyve16.S; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
108707293  fst.S; follistatin-like isoform X1 [KO:K04661]
108707339  smad4.S; mothers against decapentaplegic homolog 4 [KO:K04501]
108707343  smad7.S; mothers against decapentaplegic homolog 7 [KO:K19631]
108707514  [KO:K16622]
108707633  lrrc32.1.L; transforming growth factor beta activator LRRC32 [KO:K26316]
108707740  inhbc.2.L; inhibin beta C chain [KO:K22688]
108707936  ncor1.L; nuclear receptor corepressor 1-like isoform X9 [KO:K04650]
108708536  acvrl1.L; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
108708537  acvr1b.L; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
108708911  fmod.S; fibromodulin [KO:K08121]
108708988  acvrl1.S; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
108709130  inhbc.1.S; inhibin beta B chain [KO:K22688]
108709436  rhoc.S; rho-related GTP-binding protein RhoA-D [KO:K04513]
108709602  [KO:K16622]
108709859  inhbc.2.S; inhibin beta C chain [KO:K22688]
108709904  [KO:K04672] [EC:2.7.11.30]
108709905  sp1.S; transcription factor Sp1 [KO:K04684]
108710039  lrrc32.1.S; transforming growth factor beta activator LRRC32 [KO:K26316]
108710296  thsd4.L; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
108710348  [KO:K04666]
108710900  bmpr1b.L; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
108711076  lemd3.L; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
108711311  sin3a.L; paired amphipathic helix protein Sin3a [KO:K11644]
108711397  fbn1.L; fibrillin-1 [KO:K06825]
108711635  [KO:K04666]
108711649  [KO:K04666]
108711650  [KO:K04666]
108711816  [KO:K23910]
108712279  [KO:K04666]
108712369  [KO:K04687]
108712618  ppp2ca.S; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
108712619  skp1.S; S-phase kinase-associated protein 1 isoform X2 [KO:K03094]
108712673  nodal1.S; nodal homolog isoform X1 [KO:K04666]
108712674  [KO:K04666]
108712801  smad3.S; mothers against decapentaplegic homolog 3 [KO:K23605]
108712829  rgma.S; repulsive guidance molecule A [KO:K23096]
108712909  fbn1.S; fibrillin-1 [KO:K06825]
108712945  bmp7.2.S; bone morphogenetic protein 7-like [KO:K16621]
108712946  thsd4.S; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
108712989  neo1.S; neogenin isoform X1 [KO:K06766]
108713023  [KO:K28359]
108713078  admp.L; bone morphogenetic protein 2 [KO:K21283]
108714169  e2f4.L; transcription factor E2F4-like [KO:K04682]
108714480  ep300.L; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108714482  rbx1.L; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
108715600  zfyve9.S; zinc finger FYVE domain-containing protein 9 [KO:K04679]
108715729  ep300.S; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108715730  rbx1.S; RING-box protein 1 [KO:K03868] [EC:2.3.2.32]
108715815  rhoa.S; transforming protein RhoA [KO:K04513]
108716188  chrd.2.L; chordin-like [KO:K04657]
108716682  ltbp1.L; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
108716821  hdac2.L; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
108716914  bmp5.L; bone morphogenetic protein 5 [KO:K04663]
108716939  chrd.1.L; chordin-like [KO:K04657]
108716958  tfrc.L; transferrin receptor protein 1 [KO:K06503]
108717014  skil.L; ski-like protein [KO:K18499]
108717140  nrros.L; transforming growth factor beta activator LRRC33 [KO:K26317]
108717203  gdf7.L; growth/differentiation factor 6-A [KO:K20013]
108717359  rgmb.L; RGM domain family member B [KO:K06847]
108717655  zfyve16.L; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
108717706  tgfb2.S; transforming growth factor beta-2 proprotein-like isoform X1 [KO:K13376]
108718013  bmp5.S; bone morphogenetic protein 5 isoform X2 [KO:K04663]
108718059  tfrc.S; transferrin receptor protein 1 [KO:K06503]
108718935  tgfbr2.L; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
108718985  inhba.L; inhibin beta A chain [KO:K04667]
108719029  [KO:K04674] [EC:2.7.11.30]
108719128  bmp6.L; bone morphogenetic protein 6 [KO:K16620]
108719207  tgif1.L; homeobox protein AKR [KO:K19383]
108719215  rock1.L; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
108719317  e2f5.L; transcription factor E2F5 isoform X1 [KO:K04682]
108719358  [KO:K20012]
108719963  tgfbr2.S; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
108719965  amh.L; muellerian-inhibiting factor [KO:K04665]
108720005  inhba.S; inhibin beta A chain [KO:K04667]
373558  nodal6.L; nodal homolog 6 L homeolog precursor [KO:K04666]
373585  nodal5.2.L; nodal homolog 5, gene 2 L homeolog precursor [KO:K04666]
373586  pitx2.S; paired like homeodomain 2 S homeolog [KO:K04686]
373597  nodal3.2.L; nodal homolog 3-B precursor [KO:K04666]
373646  nog.L; noggin precursor [KO:K04658]
373697  nbl1.L; neuroblastoma suppressor of tumorigenicity 1 precursor [KO:K19558]
373733  zfyve9.L; zinc finger FYVE-type containing 9 L homeolog [KO:K04679]
373795  crebbp.S; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
373801  tgfb2.L; transforming growth factor beta-2 proprotein precursor [KO:K13376]
373815  tgfbr2l.L; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
373820  gdf7.S; growth differentiation factor 7 S homeolog precursor [KO:K20013]
373829  lefty.L; left-right determination factor L homeolog precursor [KO:K04668]
378537  nodal3.1.L; nodal homolog 3-A precursor [KO:K04666]
378543  nodal1.L; nodal homolog precursor [KO:K04666]
378633  smad3.L; SMAD family member 3 L homeolog [KO:K23605]
378661  inhbc.1.L; inhibin subunit beta C L homeolog precursor [KO:K22688]
378780  bmp2.S; bone morphogenetic protein 2-A precursor [KO:K21283]
379052  myc.S; transcriptional regulator Myc-A [KO:K04377]
379083  hdac1.S; probable histone deacetylase 1-B [KO:K06067] [EC:3.5.1.98]
379222  id3.L; DNA-binding protein inhibitor ID-3-A [KO:K17694]
379326  rhoc.L; ras homolog family member C L homeolog [KO:K04513]
379416  rhoa.L; ras homolog family member A L homeolog [KO:K04513]
379447  id3.S; DNA-binding protein inhibitor ID-3-B [KO:K17694]
379502  tf.S; serotransferrin-A precursor [KO:K14736]
379508  thbs1.L; thrombospondin 1 L homeolog precursor [KO:K16857]
379625  bmp7.2.L; bone morphogenetic protein 7 precursor [KO:K16621]
379659  smad9.S; SMAD family member 9 S homeolog [KO:K16791]
379664  smad1.L; SMAD family member 1 L homeolog [KO:K04676]
379827  ppp2r1a.L; protein phosphatase 2 regulatory subunit A, alpha L homeolog [KO:K03456]
380045  ppp2cal.S; protein phosphatase 2 catalytic subunit alpha-like S homeolog [KO:K04382] [EC:3.1.3.16]
380100  ppp2r1b.S; protein phosphatase 2 regulatory subunit A, beta S homeolog [KO:K03456]
380112  tgif1.S; TGFB induced factor homeobox 1 S homeolog [KO:K19383]
380133  rhoa.2.S; ras homolog gene family, member A, gene 2 S homeolog [KO:K04513]
380244  rgma.L; repulsive guidance molecule BMP co-receptor a L homeolog precursor [KO:K23096]
380309  emp3.L; epithelial membrane protein 3 L homeolog [KO:K26257]
380396  id4.S; DNA-binding protein inhibitor ID-4 [KO:K17695]
380538  skp1.L; S-phase kinase-associated protein 1 [KO:K03094]
380560  bmp7.1.L; bone morphogenetic protein 7, gene 1 L homeolog [KO:K16621]
394271  ski.S; ski oncogene [KO:K26503]
394276  rps6kb1.S; ribosomal protein S6 kinase B1 S homeolog [KO:K04688] [EC:2.7.11.1]
394331  smad7.L; SMAD family member 7 L homeolog [KO:K19631]
394339  ppp2r1a.S; protein phosphatase 2 regulatory subunit A, alpha S homeolog [KO:K03456]
394347  rps6kb1.L; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
394401  bambi.L; BMP and activin membrane-bound inhibitor L homeolog precursor [KO:K10162]
397711  bmpr1a.L; bone morphogenetic protein receptor type 1A L homeolog precursor [KO:K04673] [EC:2.7.11.30]
397712  bmpr1a.S; bone morphogenetic protein receptor type 1A S homeolog precursor [KO:K04673] [EC:2.7.11.30]
397778  tgfb1.L; transforming growth factor beta-1 proprotein precursor [KO:K13375]
397785  mapk1.L; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
397835  nodal2.L; nodal homolog 2-A precursor [KO:K04666]
397859  acvr2b.S; activin A receptor type 2B S homeolog precursor [KO:K13596] [EC:2.7.11.30]
397868  hdac1.L; probable histone deacetylase 1-A [KO:K06067] [EC:3.5.1.98]
397873  bmp2.L; bone morphogenetic protein 2-B precursor [KO:K21283]
397874  bmp4.L; bone morphogenetic protein 4 precursor [KO:K04662]
397981  bmpr2.S; bone morphogenetic protein receptor type II S homeolog [KO:K04671] [EC:2.7.11.30]
398033  pitx2.L; paired like homeodomain 2 L homeolog [KO:K04686]
398045  chrd.1.S; chordin precursor [KO:K04657]
398053  admp.S; anti-dorsalizing morphogenic protein S homeolog precursor [KO:K21283]
398068  nodal.L; nodal homolog 4-A precursor [KO:K04666]
398111  id2.L; DNA-binding protein inhibitor ID-2-A [KO:K17693]
398130  sin3a.S; SIN3 transcription regulator family member A S homeolog [KO:K11644]
398131  smurf1.L; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
398193  lefty.S; left-right determination factor S homeolog precursor [KO:K04668]
398304  ncor1.S; nuclear receptor corepressor 1 [KO:K04650]
398322  ltbp1.S; latent transforming growth factor beta binding protein 1 S homeolog precursor [KO:K19559]
398372  smurf2.S; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
398563  [KO:K03456]
398582  lemd3.S; LEM domain containing 3 S homeolog [KO:K19410]
398723  tf.L; serotransferrin-B precursor [KO:K14736]
398985  mapk1.S; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
399083  acvr1.S; activin A receptor type 1 S homeolog precursor [KO:K04675] [EC:2.7.11.30]
399094  grem1.L; gremlin-1 precursor [KO:K23318]
399103  acvr1.L; activin A receptor type 1 L homeolog precursor [KO:K04675] [EC:2.7.11.30]
399144  gdf6.S; growth differentiation factor 6 S homeolog precursor [KO:K20012]
399252  hdac2.S; histone deacetylase 2 S homeolog [KO:K06067] [EC:3.5.1.98]
399277  acvr2b.L; activin receptor type-2B precursor [KO:K13596] [EC:2.7.11.30]
399280  inhbb.L; inhibin subunit beta B L homeolog precursor [KO:K22687]
399282  fst.L; follistatin precursor [KO:K04661]
399283  acvr2a.L; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
399295  tgfbr1.S; transforming growth factor beta receptor I S homeolog precursor [KO:K04674] [EC:2.7.11.30]
399309  ski.L; SKI proto-oncogene L homeolog [KO:K26503]
399315  myc.L; transcriptional regulator Myc-B [KO:K04377]
399322  bmp4.S; bone morphogenetic protein 4 precursor [KO:K04662]
399343  ppp2cb.L; protein phosphatase 2, catalytic subunit, beta isozyme L homeolog [KO:K04382] [EC:3.1.3.16]
399369  smad6.L; SMAD family member 6 L homeolog [KO:K04677]
399442  smad2.L; SMAD family member 2 L homeolog [KO:K04500]
399454  acvr1b.S; activin A receptor type 1B S homeolog precursor [KO:K13567] [EC:2.7.11.30]
399457  smad1.S; SMAD family member 1 S homeolog [KO:K04676]
403356  smad4.2.L; SMAD family member 4, gene 2 L homeolog 2 [KO:K04501]
431930  rbl1.L; retinoblastoma-like 1 L homeolog [KO:K04681]
431939  sp1.L; transcription factor Sp1 isoform X2 [KO:K04684]
432023  smad2.S; SMAD family member 2 S homeolog [KO:K04500]
444234  dcn.S; decorin S homeolog precursor [KO:K04660]
446295  gdf5.L; growth differentiation factor 5 L homeolog precursor [KO:K04664]
446324  tmem53.L; transmembrane protein 53-B [KO:K28359]
446541  e2f4.S; transcription factor E2F4 [KO:K04682]
447302  bambi.S; BMP and activin membrane-bound inhibitor S homeolog precursor [KO:K10162]
447406  tfdp1.S; transcription factor Dp-1 S homeolog [KO:K04683]
447461  tgif2.L; TGFB induced factor homeobox 2 L homeolog [KO:K19553]
447463  id2.S; DNA-binding protein inhibitor ID-2-B [KO:K17693]
447470  tgif2.S; TGFB induced factor homeobox 2 S homeolog [KO:K19553]
447482  dcn.L; decorin L homeolog precursor [KO:K04660]
494744  tfdp1.L; transcription factor Dp-1 L homeolog [KO:K04683]
495087  acvr2a.S; uncharacterized protein LOC495087 precursor [KO:K04670] [EC:2.7.11.30]
495386  emp3.S; epithelial membrane protein 3 S homeolog [KO:K26257]
495689  crebbp.L; CREB binding protein L homeolog [KO:K04498] [EC:2.3.1.48]
496092  tmem53.S; transmembrane protein 53-A [KO:K28359]
503510  nog2.L; noggin 2 L homeolog precursor [KO:K04658]
734176  nodal6.S; nodal homolog 6 S homeolog precursor [KO:K04666]
734414  cul1.S; cullin 1 S homeolog [KO:K03347]
734440  bmp6.S; bone morphogenetic protein 6 S homeolog precursor [KO:K16620]
734526  cul1.L; uncharacterized protein LOC734526 [KO:K03347]
779026  thbs1.S; thrombospondin-1 [KO:K16857]
779240  cdkn2b.L; cyclin-dependent kinase inhibitor 2B L homeolog [KO:K04685]
780748  nodal5.L; nodal homolog 5 L homeolog precursor [KO:K04666]
780764  smad4.L; SMAD family member 4, gene 1 L homeolog [KO:K04501]
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
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  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
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  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
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  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
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  Title
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  Journal
Endocr Rev 25:72-101 (2004)
DOI:10.1210/er.2003-0007
Reference
PMID:11252746
  Authors
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  Title
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  Journal
Nat Rev Genet 1:171-81 (2000)
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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
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  Title
Establishment of vertebrate left-right asymmetry.
  Journal
Nat Rev Genet 3:103-13 (2002)
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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.
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Related
pathway
xla04010  MAPK signaling pathway
xla04110  Cell cycle
xla04120  Ubiquitin mediated proteolysis
xla04210  Apoptosis
KO pathway
ko04350   

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