KEGG   PATHWAY: cabi04350
Entry
cabi04350                   Pathway                                
Name
TGF-beta signaling pathway - Chelonoidis abingdonii (Abingdon island giant tortoise)
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
cabi04350  TGF-beta signaling pathway
cabi04350

Other DBs
GO: 0007179
Organism
Chelonoidis abingdonii (Abingdon island giant tortoise) [GN:cabi]
Gene
116814759  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
116814941  FBN1; fibrillin-1 [KO:K06825]
116814953  TFR2; transferrin receptor protein 2 [KO:K23910]
116815485  GDF6; growth/differentiation factor 6 [KO:K20012]
116815639  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
116815741  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
116816015  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
116816088  DCN; decorin [KO:K04660]
116816405  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
116816496  RHOA; transforming protein RhoA [KO:K04513]
116816662  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
116816796  ID1; LOW QUALITY PROTEIN: DNA-binding protein inhibitor ID-1 [KO:K04680]
116816914  GDF5; growth/differentiation factor 5 [KO:K04664]
116816947  [KO:K21283]
116817549  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
116817906  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
116818025  BMP6; bone morphogenetic protein 6 [KO:K16620]
116818558  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
116818609  TGIF2; homeobox protein TGIF2 [KO:K19553]
116818669  [KO:K14736]
116818816  GDF7; growth/differentiation factor 7 [KO:K20013]
116818851  [KO:K22688]
116818853  [KO:K22688]
116818892  [KO:K04513]
116819065  [KO:K19559]
116819415  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
116819607  BMP4; bone morphogenetic protein 4 [KO:K04662]
116820134  RGMB; RGM domain family member B [KO:K06847]
116820635  E2F5; transcription factor E2F5 [KO:K04682]
116821238  GREM2; gremlin-2 isoform X1 [KO:K23318]
116821423  [KO:K04666]
116821816  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
116821880  [KO:K04671] [EC:2.7.11.30]
116821939  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
116822306  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
116822565  HAMP; hepcidin [KO:K23106]
116822572  [KO:K23106]
116822806  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116822828  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
116822853  TNF; tumor necrosis factor isoform X1 [KO:K03156]
116823011  TFRC; transferrin receptor protein 1 [KO:K06503]
116823287  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
116823341  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
116823551  IFNG; interferon gamma [KO:K04687]
116823811  [KO:K23096]
116823822  [KO:K04668]
116824056  BMP2; bone morphogenetic protein 2 [KO:K21283]
116824341  [KO:K19558]
116824477  AMH; muellerian-inhibiting factor [KO:K04665]
116824608  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
116825005  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
116825468  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
116825530  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116825807  CUL1; cullin-1 [KO:K03347]
116825838  [KO:K21283]
116826076  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
116826173  NODAL; nodal homolog [KO:K04666]
116826358  RGMA; repulsive guidance molecule A [KO:K23096]
116826483  [KO:K04685]
116826484  [KO:K04685]
116826543  MYC; myc proto-oncogene protein [KO:K04377]
116826640  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
116826669  SKI; ski oncogene isoform X1 [KO:K26503]
116826749  SKIL; ski-like protein [KO:K18499]
116826785  [KO:K28359]
116827024  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
116827065  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
116827410  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
116827804  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
116827884  FMOD; fibromodulin [KO:K08121]
116828212  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
116828475  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
116828478  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
116829048  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116829058  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
116829153  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
116829383  GREM1; gremlin-1 [KO:K23318]
116829547  NEO1; neogenin [KO:K06766]
116829611  E2F4; transcription factor E2F4 [KO:K04682]
116829938  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
116829952  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
116830036  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
116830055  RBL1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
116830106  [KO:K04677]
116830240  [KO:K16622]
116830587  [KO:K13578] [EC:2.7.11.30]
116830588  [KO:K13578] [EC:2.7.11.30]
116830660  TGIF1; homeobox protein TGIF1 [KO:K19383]
116831627  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
116831726  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
116831861  HJV; hemojuvelin [KO:K23100]
116832335  EMP3; epithelial membrane protein 3 [KO:K26257]
116832643  INHBA; inhibin beta A chain [KO:K04667]
116832740  [KO:K04501]
116832884  [KO:K04388] [EC:2.7.11.30]
116833425  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
116833584  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
116833674  [KO:K23106]
116833884  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
116834017  INHBB; inhibin beta B chain [KO:K22687]
116834470  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
116834698  [KO:K26316]
116835549  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
116835779  FST; follistatin [KO:K04661]
116836027  [KO:K04658]
116836248  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
116837512  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
116837806  THBS1; thrombospondin-1 [KO:K16857]
116837968  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
116838268  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
116838546  CHRD; chordin [KO:K04657]
116839290  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
116839551  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
116839576  NOG; noggin [KO:K04658]
116839745  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
116839798  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
116840017  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
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
cabi04010  MAPK signaling pathway
cabi04110  Cell cycle
cabi04120  Ubiquitin mediated proteolysis
cabi04210  Apoptosis
KO pathway
ko04350   

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