KEGG   PATHWAY: phi04350
Entry
phi04350                    Pathway                                
Name
TGF-beta signaling pathway - Pseudopodoces humilis (Tibetan ground-tit)
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
phi04350  TGF-beta signaling pathway
phi04350

Other DBs
GO: 0007179
Organism
Pseudopodoces humilis (Tibetan ground-tit) [GN:phi]
Gene
102099074  IFNG; interferon gamma [KO:K04687]
102099118  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102099184  INHBC; inhibin beta C chain [KO:K22688]
102099204  [KO:K04388] [EC:2.7.11.30]
102099543  [KO:K22689]
102099547  GDF5; growth/differentiation factor 5 [KO:K04664]
102099570  GDF7; growth/differentiation factor 7 [KO:K20013]
102099633  ID4; DNA-binding protein inhibitor ID-4 isoform X2 [KO:K17695]
102099713  FMOD; fibromodulin [KO:K08121]
102099878  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102099916  RGMB; RGM domain family member B [KO:K06847]
102100046  GDF6; growth/differentiation factor 6 [KO:K20012]
102100143  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
102100299  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102100457  TFR2; transferrin receptor protein 2 [KO:K23910]
102100544  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
102100590  CUL1; cullin-1 isoform X2 [KO:K03347]
102100671  TFRC; transferrin receptor protein 1 [KO:K06503]
102100805  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102100951  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
102100992  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
102101166  BMP6; bone morphogenetic protein 6 [KO:K16620]
102101225  BMP2; bone morphogenetic protein 2 [KO:K21283]
102101691  E2F5; transcription factor E2F5 [KO:K04682]
102101767  RGMA; repulsive guidance molecule A [KO:K23096]
102101806  [KO:K04677]
102102028  [KO:K19558]
102102087  [KO:K26316]
102102248  TGFB3; transforming growth factor beta-3 [KO:K13377]
102102303  GREM1; gremlin-1 [KO:K23318]
102102573  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
102102648  INHBA; inhibin beta A chain [KO:K04667]
102102768  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102102779  TGIF2; homeobox protein TGIF2 [KO:K19553]
102102817  [KO:K26316]
102102818  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102102832  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102102996  FBN1; fibrillin-1 [KO:K06825]
102103012  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
102103022  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102103315  SKIL; ski-like protein [KO:K18499]
102103337  RBL1; retinoblastoma-like protein 1 isoform X3 [KO:K04681]
102103410  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
102103434  CHRD; chordin isoform X1 [KO:K04657]
102103663  THBS1; thrombospondin-1 [KO:K16857]
102103664  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
102103796  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
102103977  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
102104194  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
102104230  SKI; ski oncogene [KO:K26503]
102104637  RHOA; transforming protein RhoA [KO:K04513]
102104750  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102105581  FST; follistatin [KO:K04661]
102105645  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
102106092  BMP5; bone morphogenetic protein 5 [KO:K04663]
102107002  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
102107017  HFE2; hemojuvelin isoform X2 [KO:K23100]
102107051  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X4 [KO:K04678] [EC:2.3.2.26]
102107072  NRROS; negative regulator of reactive oxygen species [KO:K26317]
102107167  NEO1; neogenin [KO:K06766]
102107181  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
102107184  NOG; noggin [KO:K04658]
102107738  TF; serotransferrin [KO:K14736]
102107771  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
102107806  AMH; muellerian-inhibiting factor [KO:K04665]
102107888  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
102108348  RPS6KB2; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
102108638  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
102108851  MYC; myc proto-oncogene protein [KO:K04377]
102109205  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102109412  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
102109524  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
102110190  INHBB; inhibin beta B chain [KO:K22687]
102110191  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
102110252  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
102110411  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
102110438  GREM2; gremlin-2 isoform X2 [KO:K23318]
102110458  BMP7; bone morphogenetic protein 7 [KO:K16621]
102110472  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
102110637  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
102110827  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102110926  [KO:K04666]
102111222  [KO:K04685]
102111403  [KO:K04685]
102111680  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
102111754  [KO:K21283]
102111851  [KO:K04501]
102112160  PITX2; pituitary homeobox 2 isoform X2 [KO:K04686]
102112281  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102112711  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102112781  TGFB1; transforming growth factor beta-1 [KO:K13375]
102112801  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
102112804  [KO:K04658]
102113016  [KO:K16622]
102113049  DCN; decorin [KO:K04660]
102113091  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
102113133  [KO:K19559]
102113162  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
102113171  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
102113190  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
102113332  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
102113643  [KO:K21283]
102113677  LEFTY1; left-right determination factor 1 [KO:K04668]
102113684  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
102113882  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
102114343  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
102114598  TGFB2; transforming growth factor beta-2 [KO:K13376]
106628971  HAMP; hepcidin [KO:K23106]
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
phi04010  MAPK signaling pathway
phi04110  Cell cycle
phi04120  Ubiquitin mediated proteolysis
phi04210  Apoptosis
KO pathway
ko04350   

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