KEGG   PATHWAY: shr04350
Entry
shr04350                    Pathway                                
Name
TGF-beta signaling pathway - Sarcophilus harrisii (Tasmanian devil)
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
shr04350  TGF-beta signaling pathway
shr04350

Other DBs
GO: 0007179
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100913322  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100913352  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100913702  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
100913813  RGMA; repulsive guidance molecule A [KO:K23096]
100913844  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100914254  BMP7; bone morphogenetic protein 7 [KO:K16621]
100914315  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
100914910  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
100914956  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100915162  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
100915523  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
100915554  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
100915670  [KO:K14736]
100915856  SKI; LOW QUALITY PROTEIN: ski oncogene [KO:K26503]
100915869  GREM2; gremlin-2 [KO:K23318]
100916021  [KO:K16622]
100916171  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
100916609  BMP4; bone morphogenetic protein 4 [KO:K04662]
100916611  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
100917391  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
100917689  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
100917723  GREM1; gremlin-1 [KO:K23318]
100917741  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
100918404  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100918537  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
100918755  NODAL; nodal homolog [KO:K04666]
100919390  AMH; muellerian-inhibiting factor [KO:K04665]
100919412  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
100920078  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
100920492  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100920613  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
100921187  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100921308  MYC; myc proto-oncogene protein [KO:K04377]
100921630  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100921722  NEO1; neogenin isoform X1 [KO:K06766]
100921875  TNF; tumor necrosis factor [KO:K03156]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100921980  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100922131  FMOD; fibromodulin [KO:K08121]
100922470  NOG; noggin [KO:K04658]
100922547  INHBB; inhibin beta B chain [KO:K22687]
100922551  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100922940  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
100923094  DCN; decorin isoform X1 [KO:K04660]
100923201  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
100923569  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100924021  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100924661  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
100924755  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
100924883  INHBA; inhibin beta A chain [KO:K04667]
100925177  SKIL; ski-like protein [KO:K18499]
100925261  [KO:K14736]
100925611  [KO:K04668]
100925781  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
100926283  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
100926417  CUL1; cullin-1 [KO:K03347]
100926537  RGMB; RGM domain family member B isoform X1 [KO:K06847]
100926696  FBN1; fibrillin-1 isoform X1 [KO:K06825]
100926698  THBS1; thrombospondin-1 [KO:K16857]
100927043  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100927161  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100927300  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100927352  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100928279  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
100928319  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100929022  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100929520  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
100929544  BMP6; bone morphogenetic protein 6 [KO:K16620]
100929617  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
100929699  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100929763  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
100929797  GDF6; growth/differentiation factor 6 [KO:K20012]
100930024  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
100930117  INHBC; inhibin beta C chain [KO:K22688]
100930374  INHBE; inhibin beta E chain [KO:K22689]
100930409  FST; follistatin isoform X1 [KO:K04661]
100930564  GDF5; growth/differentiation factor 5 [KO:K04664]
100930707  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X2 [KO:K04688] [EC:2.7.11.1]
100930864  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
100931037  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
100931700  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X2 [KO:K23377]
100931897  E2F4; transcription factor E2F4 [KO:K04682]
100932002  [KO:K19558]
100932026  BMP5; bone morphogenetic protein 5 [KO:K04663]
100932607  TGFB1; LOW QUALITY PROTEIN: transforming growth factor beta-1 proprotein [KO:K13375]
100932648  [KO:K04382] [EC:3.1.3.16]
100933428  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
100933894  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
100934041  [KO:K26316]
100934195  CHRD; chordin isoform X1 [KO:K04657]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100935081  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100935094  BMP2; bone morphogenetic protein 2 [KO:K21283]
105749936  HAMP; hepcidin isoform X2 [KO:K23106]
105750182  [KO:K26168]
105750683  IFNG; interferon gamma [KO:K04687]
105751089  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
111719098  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
111720150  EMP3; epithelial membrane protein 3 [KO:K26257]
111720196  [KO:K26168]
111720748  HJV; hemojuvelin [KO:K23100]
116419459  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
116421208  GDF7; growth/differentiation factor 7 [KO:K20013]
116421719  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
116422822  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
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
shr04010  MAPK signaling pathway
shr04110  Cell cycle
shr04120  Ubiquitin mediated proteolysis
shr04210  Apoptosis
KO pathway
ko04350   

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