KEGG   PATHWAY: aamp04350
Entry
aamp04350                   Pathway                                
Name
TGF-beta signaling pathway - Arvicola amphibius (Eurasian water vole)
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
aamp04350  TGF-beta signaling pathway
aamp04350

Other DBs
GO: 0007179
Organism
Arvicola amphibius (Eurasian water vole) [GN:aamp]
Gene
119800048  Bmp4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
119800845  Hjv; hemojuvelin isoform X1 [KO:K23100]
119800949  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
119801261  Pitx2; pituitary homeobox 2 isoform X1 [KO:K04686]
119801675  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
119801903  E2f4; transcription factor E2F4 [KO:K04682]
119802832  Emp3; epithelial membrane protein 3 [KO:K26257]
119803004  Rgma; repulsive guidance molecule A [KO:K23096]
119803038  Lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
119803395  Dcn; decorin [KO:K04660]
119803426  Inhbe; inhibin beta E chain [KO:K22689]
119803519  Lemd3; inner nuclear membrane protein Man1 [KO:K19410]
119803595  Inhbc; LOW QUALITY PROTEIN: inhibin beta C chain [KO:K22688]
119803682  Ifng; interferon gamma [KO:K04687]
119803828  Tgif1; homeobox protein TGIF1 isoform X1 [KO:K19383]
119804001  Bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
119804987  Igsf1; immunoglobulin superfamily member 1 [KO:K26168]
119805946  Amh; muellerian-inhibiting factor [KO:K04665]
119806685  Cul1; cullin-1 [KO:K03347]
119806758  Gdf7; LOW QUALITY PROTEIN: growth/differentiation factor 7 [KO:K20013]
119807084  Ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
119807598  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
119807840  [KO:K04513]
119809060  Zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
119809678  Thsd4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
119809718  Bmp5; bone morphogenetic protein 5 [KO:K04663]
119809769  Acvr2b; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
119809780  Smad6; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 6 [KO:K04677]
119809827  Neo1; neogenin isoform X1 [KO:K06766]
119809845  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
119810133  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
119810276  [KO:K14736]
119810277  Tf; serotransferrin [KO:K14736]
119810440  Sin3a; LOW QUALITY PROTEIN: paired amphipathic helix protein Sin3a [KO:K11644]
119810460  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
119810493  Rhoa; transforming protein RhoA [KO:K04513]
119810670  Fst; follistatin isoform X1 [KO:K04661]
119811147  Ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
119811275  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
119811297  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
119811558  [KO:K04498] [EC:2.3.1.48]
119812170  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
119812769  Skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
119812787  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
119813254  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
119813356  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119813710  Nog; noggin [KO:K04658]
119814141  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
119814185  Tgif2; homeobox protein TGIF2 isoform X1 [KO:K19553]
119814203  Rock1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
119814518  Bmp2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
119814594  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
119814613  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
119814660  Fbn1; fibrillin-1 [KO:K06825]
119814744  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
119814841  Bmp7; bone morphogenetic protein 7 [KO:K16621]
119814876  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
119815066  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
119815510  Thbs1; thrombospondin-1 [KO:K16857]
119815687  Grem1; gremlin-1 isoform X1 [KO:K23318]
119815851  Gdf5; growth/differentiation factor 5 [KO:K04664]
119816116  Zfyve9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
119816323  Bmp6; bone morphogenetic protein 6 [KO:K16620]
119816364  Nbl1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
119816394  Inhba; LOW QUALITY PROTEIN: inhibin beta A chain [KO:K04667]
119816522  Hfe; hereditary hemochromatosis protein isoform X1 [KO:K26535]
119816689  Smad5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
119816774  Bambi; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
119816884  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
119816915  Ski; ski oncogene isoform X1 [KO:K26503]
119817062  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
119817074  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
119817308  [KO:K16622]
119817395  Tmem53; transmembrane protein 53 isoform X1 [KO:K28359]
119817430  [KO:K04685]
119817859  Bmp8a; bone morphogenetic protein 8A [KO:K16622]
119818383  Acvr2a; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
119819021  Acvr1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
119819138  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
119819331  Acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
119820564  [KO:K03094]
119820706  [KO:K06067] [EC:3.5.1.98]
119820755  [KO:K06067] [EC:3.5.1.98]
119820797  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
119820825  [KO:K23106]
119820863  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
119821456  Tgfb1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
119821579  Rgmb; RGM domain family member B [KO:K06847]
119822506  Tnf; tumor necrosis factor [KO:K03156]
119822927  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
119822940  Myc; myc proto-oncogene protein [KO:K04377]
119823040  Acvr1b; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
119823260  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
119823435  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
119823477  Amhr2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
119823927  Nodal; nodal homolog [KO:K04666]
119824680  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119824741  Tfrc; transferrin receptor protein 1 isoform X1 [KO:K06503]
119824777  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
119824917  Tfr2; LOW QUALITY PROTEIN: transferrin receptor protein 2 [KO:K23910]
119825510  Nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
119825720  Chrd; chordin isoform X1 [KO:K04657]
119825895  Gdf6; growth/differentiation factor 6 [KO:K20012]
119826233  Skil; ski-like protein isoform X1 [KO:K18499]
119826264  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
119826327  E2f5; transcription factor E2F5 [KO:K04682]
119826519  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
119827432  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
119827530  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
119827716  Fmod; fibromodulin [KO:K08121]
119827721  Inhbb; inhibin beta B chain [KO:K22687]
119827989  Grem2; gremlin-2 isoform X1 [KO:K23318]
119828074  [KO:K04668]
119828076  Lefty1; left-right determination factor 1 isoform X1 [KO:K04668]
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
aamp04010  MAPK signaling pathway
aamp04110  Cell cycle
aamp04120  Ubiquitin mediated proteolysis
aamp04210  Apoptosis
KO pathway
ko04350   

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