KEGG   PATHWAY: aam04350
Entry
aam04350                    Pathway                                
Name
TGF-beta signaling pathway - Apteryx mantelli mantelli (North Island brown kiwi)
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
aam04350  TGF-beta signaling pathway
aam04350

Other DBs
GO: 0007179
Organism
Apteryx mantelli mantelli (North Island brown kiwi) [GN:aam]
Gene
106493110  noggin [KO:K04658]
106493112  noggin [KO:K04658]
106487367  NBL1; neuroblastoma 1, DAN family BMP antagonist [KO:K19558]
106483145  GREM1; gremlin 1, DAN family BMP antagonist [KO:K23318]
106485570  GREM2; gremlin 2, DAN family BMP antagonist [KO:K23318]
106482797  THBS1; thrombospondin 1 [KO:K16857]
106488654  DCN; decorin [KO:K04660]
106483945  FMOD; fibromodulin [KO:K08121]
106482737  left-right determination factor 1-like [KO:K04668]
106494556  FST; follistatin [KO:K04661]
106490352  BMP2; bone morphogenetic protein 2 [KO:K21283]
106497809  bone morphogenetic protein 7-like [KO:K21283]
106498530  bone morphogenetic protein 2-like [KO:K21283]
106494596  BMP4; bone morphogenetic protein 4 [KO:K04662]
106500447  BMP6; bone morphogenetic protein 6 [KO:K16620]
106499052  INHBB; inhibin beta B subunit [KO:K22687]
106492614  TF; transferrin [KO:K14736]
106493255  BMP5; bone morphogenetic protein 5 [KO:K04663]
106491732  BMP7; bone morphogenetic protein 7 [KO:K16621]
106499905  GDF5; growth differentiation factor 5 [KO:K04664]
106483860  GDF6; growth differentiation factor 6 [KO:K20012]
106486430  growth/differentiation factor 7-like [KO:K20013]
106489521  muellerian-inhibiting factor-like [KO:K04665]
106489527  AMH; anti-Mullerian hormone [KO:K04665]
106488479  IFNG; interferon gamma [KO:K04687]
106496472  THSD4; thrombospondin type 1 domain containing 4 [KO:K23377]
106496465  FBN1; fibrillin 1 [KO:K06825]
106485480  LTBP1; latent transforming growth factor beta binding protein 1 [KO:K19559]
106490440  TGFB2; transforming growth factor beta 2 [KO:K13376]
106482877  TGFB3; transforming growth factor beta 3 [KO:K13377]
106495279  INHBA; inhibin beta A subunit [KO:K04667]
106482148  INHBC; inhibin beta C subunit [KO:K22688]
106482155  inhibin beta C chain-like [KO:K22688]
106496079  nodal homolog [KO:K04666]
106499867  BMPR1A; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
106491882  BMPR1B; bone morphogenetic protein receptor type 1B [KO:K13578] [EC:2.7.11.30]
106486557  ACVR1; activin A receptor type 1 [KO:K04675] [EC:2.7.11.30]
106492422  BMPR2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
106498516  ACVR2A; activin A receptor type 2A [KO:K04670] [EC:2.7.11.30]
106495951  HFE2; hemochromatosis type 2 (juvenile) [KO:K23100]
106486121  NEO1; neogenin 1 [KO:K06766]
106498260  TFRC; transferrin receptor [KO:K06503]
106482515  RGMA; repulsive guidance molecule family member a [KO:K23096]
106486414  repulsive guidance molecule A-like [KO:K23096]
106495084  RGMB; repulsive guidance molecule family member b [KO:K06847]
106491015  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
106491249  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
106498480  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
106490808  LRRC32; leucine rich repeat containing 32 [KO:K26316]
106484142  leucine-rich repeat-containing protein 32-like [KO:K26316]
106492618  NRROS; negative regulator of reactive oxygen species [KO:K26317]
106499430  ACVR1B; activin A receptor type 1B [KO:K13567] [EC:2.7.11.30]
106490270  ACVR2B; activin A receptor type 2B [KO:K13596] [EC:2.7.11.30]
106486546  ACVR1C; activin A receptor type 1C [KO:K13568] [EC:2.7.11.30]
106490029  BAMBI; BMP and activin membrane bound inhibitor [KO:K10162]
106492006  SMAD1; SMAD family member 1 [KO:K04676]
106487236  SMAD5; SMAD family member 5 [KO:K16790]
106500358  SMAD9; SMAD family member 9 [KO:K16791]
106497650  SMAD2; SMAD family member 2 [KO:K04500]
106487670  SMAD3; SMAD family member 3 [KO:K23605]
106494875  SMAD4; SMAD family member 4 [KO:K04501]
106487651  SMAD6; SMAD family member 6 [KO:K04677]
106500070  SMAD7; SMAD family member 7 [KO:K19631]
106496882  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
106493128  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
106491075  ZFYVE9; zinc finger FYVE-type containing 9 [KO:K04679]
106485022  zinc finger FYVE domain-containing protein 16-like [KO:K04679]
106488968  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
106495275  CUL1; cullin 1 [KO:K03347]
106487187  SKP1; S-phase kinase associated protein 1 [KO:K03094]
106486864  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106491145  RHOA; ras homolog family member A [KO:K04513]
106484740  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
106487221  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
106494814  uncharacterized LOC106494814 [KO:K04382] [EC:3.1.3.16]
106492594  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
106500339  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
106494736  ID2; inhibitor of DNA binding 2, HLH protein [KO:K17693]
106499916  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
106496261  E2F5; E2F transcription factor 5 [KO:K04682]
106484508  E2F4; E2F transcription factor 4 [KO:K04682]
106494055  TFDP1; transcription factor Dp-1 [KO:K04683]
106482329  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
106488223  histone acetyltransferase p300-like [KO:K04498] [EC:2.3.1.48]
106487505  SP1; Sp1 transcription factor [KO:K04684]
106486594  SKIL; SKI like proto-oncogene [KO:K18499]
106485756  ski oncogene [KO:K26503]
106485757  ski oncogene-like [KO:K26503]
106496547  SIN3A; SIN3 transcription regulator family member A [KO:K11644]
106493331  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
106489693  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
106493755  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
106484575  homeobox protein AKR [KO:K19383]
106499901  TGIF2; TGFB induced factor homeobox 2 [KO:K19553]
106496220  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
106492134  PITX2; paired like homeodomain 2 [KO:K04686]
Compound
C14819  Fe3+
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Anderson GJ, Frazer DM
  Title
Iron metabolism meets signal transduction.
  Journal
Nat Genet 38:503-4 (2006)
DOI:10.1038/ng0506-503
Reference
  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
  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
  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
  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
  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
  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
aam04010  MAPK signaling pathway
aam04110  Cell cycle
aam04120  Ubiquitin mediated proteolysis
aam04210  Apoptosis
KO pathway
ko04350   
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