KEGG   PATHWAY: ccan04350
Entry
ccan04350                   Pathway                                
Name
TGF-beta signaling pathway - Castor canadensis (American beaver)
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
ccan04350  TGF-beta signaling pathway
ccan04350

Other DBs
GO: 0007179
Organism
Castor canadensis (American beaver) [GN:ccan]
Gene
109694097  Chrd; LOW QUALITY PROTEIN: chordin [KO:K04657]
109700721  Nog; noggin [KO:K04658]
109687471  Nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
109673950  Grem2; gremlin-2 [KO:K23318]
109701240  Grem1; gremlin-1 isoform X1 [KO:K23318]
109700113  Thbs1; thrombospondin-1 [KO:K16857]
109698283  Dcn; decorin [KO:K04660]
109699667  Fmod; fibromodulin [KO:K08121]
109691491  left-right determination factor 2-like isoform X1 [KO:K04668]
109691493  left-right determination factor 2-like isoform X1 [KO:K04668]
109691801  Fst; follistatin isoform X1 [KO:K04661]
109677386  Bmp2; bone morphogenetic protein 2 [KO:K21283]
109701382  Bmp4; bone morphogenetic protein 4 [KO:K04662]
109692215  Bmp6; bone morphogenetic protein 6 [KO:K16620]
109693805  Inhbb; LOW QUALITY PROTEIN: inhibin beta B chain [KO:K22687]
109687714  inhibitor of carbonic anhydrase-like [KO:K14736]
109687722  LOW QUALITY PROTEIN: serotransferrin-like [KO:K14736]
109677097  Bmp5; LOW QUALITY PROTEIN: bone morphogenetic protein 5 [KO:K04663]
109690684  Bmp7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
109697321  bone morphogenetic protein 8B-like isoform X1 [KO:K16622]
109691571  bone morphogenetic protein 8B isoform X1 [KO:K16622]
109681889  Gdf5; growth/differentiation factor 5 [KO:K04664]
109677714  Gdf6; growth/differentiation factor 6 [KO:K20012]
109681734  Gdf7; growth/differentiation factor 7 isoform X1 [KO:K20013]
109689925  Amh; muellerian-inhibiting factor [KO:K04665]
109676142  Ifng; interferon gamma [KO:K04687]
109690391  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
109701737  Thsd4; LOW QUALITY PROTEIN: thrombospondin type-1 domain-containing protein 4 [KO:K23377]
109684261  Fbn1; fibrillin-1 [KO:K06825]
109694260  Ltbp1; LOW QUALITY PROTEIN: latent-transforming growth factor beta-binding protein 1 [KO:K19559]
109685632  Tgfb1; transforming growth factor beta-1 [KO:K13375]
109698650  Tgfb2; transforming growth factor beta-2 isoform X1 [KO:K13376]
109686152  Tgfb3; transforming growth factor beta-3 [KO:K13377]
109676338  Inhba; inhibin beta A chain [KO:K04667]
109686006  Inhbc; inhibin beta C chain [KO:K22688]
109686168  Inhbe; inhibin beta E chain [KO:K22689]
109685028  Nodal; nodal homolog [KO:K04666]
109684779  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
109703066  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
109688929  Acvr1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
109683698  Bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
109689204  Acvr2a; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
109694615  Hfe2; hemojuvelin isoform X1 [KO:K23100]
109687655  Neo1; LOW QUALITY PROTEIN: neogenin [KO:K06766]
109677169  Hfe; hereditary hemochromatosis protein isoform X1 [KO:K26535]
109701435  Tfr2; transferrin receptor protein 2 [KO:K23910]
109694497  Tfrc; transferrin receptor protein 1 isoform X1 [KO:K06503]
109701540  Rgma; repulsive guidance molecule A isoform X1 [KO:K23096]
109691217  Rgmb; RGM domain family member B [KO:K06847]
109684090  Amhr2; LOW QUALITY PROTEIN: anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
109691424  Tgfbr1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
109681522  Tgfbr2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
109699902  Emp3; epithelial membrane protein 3 [KO:K26257]
109688572  Lrrc32; leucine-rich repeat-containing protein 32 [KO:K26316]
109694506  Nrros; negative regulator of reactive oxygen species [KO:K26317]
109685525  Acvr1b; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
109695728  Acvr2b; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
109688925  Acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
109675438  Igsf1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
109702310  Bambi; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
109688892  mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
109697355  Smad5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
109699594  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
109700302  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 2-like [KO:K04500]
109701514  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
109687032  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
109676022  mothers against decapentaplegic homolog 6-like [KO:K04677]
109676023  Smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
109683625  Smad7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
109684429  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
109695587  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
109688805  zinc finger FYVE domain-containing protein 9 [KO:K04679]
109694406  Zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
109686914  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
109695511  Cul1; cullin-1 [KO:K03347]
109689481  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
109683259  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109684381  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
109697844  Rhoa; transforming protein RhoA [KO:K04513]
109690388  transforming protein RhoA-like isoform X1 [KO:K04513]
109689990  Rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
109687790  Ppp2r1b; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
109699358  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109692163  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109689490  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109688624  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
109685124  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
109689583  Hamp; hepcidin [KO:K23106]
109691793  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
109700135  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
109693807  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
109696699  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
109693733  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
109694031  E2f4; transcription factor E2F4 [KO:K04682]
109698488  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
109682077  transcription factor E2F5-like [KO:K04682]
109686939  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
109681682  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109690951  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109684073  Sp1; transcription factor Sp1 [KO:K04684]
109700213  Skil; ski-like protein isoform X1 [KO:K18499]
109691440  Ski; ski oncogene isoform X1 [KO:K26503]
109694116  Sin3a; LOW QUALITY PROTEIN: paired amphipathic helix protein Sin3a [KO:K11644]
109692991  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
109682730  Hdac2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
109699495  Ncor1; nuclear receptor corepressor 1 [KO:K04650]
109701147  Tgif1; homeobox protein TGIF1 [KO:K19383]
109693739  Tgif2; homeobox protein TGIF2 [KO:K19553]
109699943  Myc; myc proto-oncogene protein [KO:K04377]
109701109  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
109700432  pituitary homeobox 2 isoform X1 [KO:K04686]
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
ccan04010  MAPK signaling pathway
ccan04110  Cell cycle
ccan04120  Ubiquitin mediated proteolysis
ccan04210  Apoptosis
KO pathway
ko04350   
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