KEGG   PATHWAY: acat04350
Entry
acat04350                   Pathway                                
Name
TGF-beta signaling pathway - Aquarana catesbeiana (American bullfrog)
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
acat04350  TGF-beta signaling pathway
acat04350

Other DBs
GO: 0007179
Organism
Aquarana catesbeiana (American bullfrog) [GN:acat]
Gene
141102739  RHOA; transforming protein RhoA [KO:K04513]
141103310  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
141103312  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
141103673  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
141103909  TMEM53; transmembrane protein 53 [KO:K28359]
141104171  [KO:K21283]
141105310  [KO:K04666]
141106186  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
141106187  AMH; muellerian-inhibiting factor [KO:K04665]
141106490  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
141107607  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
141107613  [KO:K03156]
141107742  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
141108294  [KO:K04513]
141108818  [KO:K26316]
141109847  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
141110268  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
141110465  [KO:K23106]
141110466  [KO:K23106]
141110528  [KO:K03456]
141110751  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
141110797  [KO:K03456]
141110937  EMP3; epithelial membrane protein 3 [KO:K26257]
141111047  SKI; ski oncogene isoform X1 [KO:K26503]
141112097  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
141112622  E2F4; transcription factor E2F4 [KO:K04682]
141113288  RBL1; retinoblastoma-like protein 1 [KO:K04681]
141113392  TGIF2; homeobox protein TGIF2 [KO:K19553]
141113495  NOG; noggin [KO:K04658]
141113835  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
141113884  BMP7; bone morphogenetic protein 7 [KO:K16621]
141114515  GDF5; growth/differentiation factor 5 [KO:K04664]
141116431  [KO:K04677]
141116493  HJV; hemojuvelin [KO:K23100]
141116745  [KO:K04501]
141116864  THBS1; thrombospondin-1 [KO:K16857]
141117475  GREM1; gremlin-1 [KO:K23318]
141117488  BMP4; bone morphogenetic protein 4 [KO:K04662]
141126854  LRRC32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
141127106  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
141127292  SP1; transcription factor Sp1 [KO:K04684]
141127407  [KO:K22688]
141127409  [KO:K22688]
141127543  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
141127544  ACVRL1; activin receptor type-1-like [KO:K04675] [EC:2.7.11.30]
141127782  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
141128155  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
141128165  [KO:K16622]
141128214  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
141128436  RHOC; rho-related GTP-binding protein RhoC [KO:K04513]
141128743  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
141129095  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
141129818  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
141131225  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
141131226  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
141131289  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
141131497  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
141131587  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
141131614  NEO1; neogenin isoform X1 [KO:K06766]
141131690  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
141131716  [KO:K28359]
141131729  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
141131947  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
141132095  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
141132127  DCN; decorin [KO:K04660]
141132422  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
141132423  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
141133158  FST; follistatin isoform X1 [KO:K04661]
141133638  TFR2; transferrin receptor protein 2 [KO:K23910]
141133908  FBN1; fibrillin-1 [KO:K06825]
141134031  [KO:K04666]
141134032  [KO:K04666]
141134035  [KO:K04666]
141134036  [KO:K04666]
141134037  [KO:K04666]
141134038  [KO:K04666]
141134039  [KO:K04666]
141134040  [KO:K04666]
141134453  [KO:K16621]
141134517  IFNG; interferon gamma [KO:K04687]
141134675  [KO:K04666]
141134676  [KO:K04666]
141134677  [KO:K04666]
141134678  [KO:K04666]
141134679  [KO:K04666]
141134680  [KO:K04666]
141134681  [KO:K04666]
141134682  [KO:K04666]
141134683  [KO:K04666]
141134684  [KO:K04666]
141134685  [KO:K04666]
141134687  [KO:K04666]
141134688  [KO:K04666]
141134689  [KO:K04666]
141134690  [KO:K04666]
141134691  [KO:K04666]
141134692  [KO:K04666]
141134693  [KO:K04666]
141134698  [KO:K04666]
141135430  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
141137168  RGMB; repulsive guidance molecule B isoform X1 [KO:K06847]
141139326  GDF7; growth/differentiation factor 7 [KO:K20013]
141139382  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
141139450  [KO:K14736]
141139451  [KO:K14736]
141139453  [KO:K14736]
141139454  [KO:K14736]
141139467  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
141139758  SKIL; ski-like protein isoform X1 [KO:K18499]
141139891  TFRC; transferrin receptor protein 1 [KO:K06503]
141139956  CHRD; chordin [KO:K04657]
141140000  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
141140204  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
141140487  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
141140852  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
141140997  BMP2; bone morphogenetic protein 2 [KO:K21283]
141141025  [KO:K04657]
141141196  [KO:K04666]
141141353  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
141141599  [KO:K04668]
141144302  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
141144513  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
141144601  CUL1; cullin-1 isoform X1 [KO:K03347]
141144645  INHBA; inhibin beta A chain [KO:K04667]
141144741  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
141144915  BMP6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
141144967  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
141145082  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
141145100  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
141145321  E2F5; transcription factor E2F5 [KO:K04682]
141145379  GDF6; growth/differentiation factor 6 [KO:K20012]
141145501  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
141145949  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
141146750  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
141147070  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
141147071  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
141147111  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
141147262  INHBB; inhibin beta B chain [KO:K22687]
141147306  [KO:K04388] [EC:2.7.11.30]
141148811  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
141148843  [KO:K04658]
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
acat04010  MAPK signaling pathway
acat04110  Cell cycle
acat04120  Ubiquitin mediated proteolysis
acat04210  Apoptosis
KO pathway
ko04350   

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