KEGG   PATHWAY: apla04350
Entry
apla04350                   Pathway                                
Name
TGF-beta signaling pathway - Anas platyrhynchos (mallard)
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
apla04350  TGF-beta signaling pathway
apla04350

Other DBs
GO: 0007179
Organism
Anas platyrhynchos (mallard) [GN:apla]
Gene
101789646  [KO:K04668]
101789702  GREM1; gremlin-1 [KO:K23318]
101789778  FMOD; fibromodulin [KO:K08121]
101789784  ACVR2A; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
101789810  BMP7; bone morphogenetic protein 7 [KO:K16621]
101790439  IFNG; interferon gamma precursor [KO:K04687]
101790663  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
101791084  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
101791115  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
101791121  [KO:K13596] [EC:2.7.11.30]
101791584  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
101791591  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
101791663  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
101792001  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
101792191  GREM2; gremlin-2 [KO:K23318]
101792754  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
101792883  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101793264  CUL1; cullin-1 [KO:K03347]
101793322  THBS1; thrombospondin-1 [KO:K16857]
101793485  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
101793506  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101793707  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101793792  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101794028  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
101794148  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
101794439  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
101794578  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
101794795  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
101794826  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
101795209  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101795303  TF; serotransferrin [KO:K14736]
101795448  INHBA; inhibin beta A chain [KO:K04667]
101795825  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101796040  RBX1; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101796147  NOG; noggin [KO:K04658]
101796241  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101796504  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
101796697  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
101796895  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
101796903  [KO:K21283]
101797112  NEO1; neogenin isoform X1 [KO:K06766]
101797330  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
101797910  RHOA; transforming protein RhoA [KO:K04513]
101798014  FBN1; fibrillin-1 isoform X2 [KO:K06825]
101798108  [KO:K04666]
101798583  TMEM53; transmembrane protein 53 [KO:K28359]
101798636  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101798837  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
101799588  RGMA; repulsive guidance molecule A [KO:K23096]
101799868  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
101799879  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101800033  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101800239  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
101800319  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101800492  INHBB; inhibin beta B chain [KO:K22687]
101800651  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
101800741  SKI; ski oncogene [KO:K26503]
101800809  [KO:K04498] [EC:2.3.1.48]
101801194  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
101801230  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
101801233  ID3; LOW QUALITY PROTEIN: DNA-binding protein inhibitor ID-3 [KO:K17694]
101801328  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
101801454  SKIL; ski-like protein [KO:K18499]
101801481  RGMB; RGM domain family member B [KO:K06847]
101801641  [KO:K04388] [EC:2.7.11.30]
101801962  DCN; decorin [KO:K04660]
101802068  AMH; muellerian-inhibiting factor precursor [KO:K04665]
101802287  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101802339  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
101802543  [KO:K19558]
101802885  FST; follistatin isoform X1 [KO:K04661]
101803068  TFRC; transferrin receptor protein 1 [KO:K06503]
101803077  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
101803206  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101803370  MYC; myc proto-oncogene protein [KO:K04377]
101803413  SKP1; LOW QUALITY PROTEIN: S-phase kinase-associated protein 1 [KO:K03094]
101803434  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
101803787  [KO:K04500]
101803850  [KO:K22688]
101803883  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X2 [KO:K04678] [EC:2.3.2.26]
101804730  BMP6; bone morphogenetic protein 6 [KO:K16620]
101804736  BMP8A; bone morphogenetic protein 8A isoform X1 [KO:K16622]
101805266  GDF5; growth/differentiation factor 5 [KO:K04664]
101805274  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101805328  [KO:K04674] [EC:2.7.11.30]
101805334  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
106016176  BMP2; bone morphogenetic protein 2 [KO:K21283]
106017909  [KO:K21283]
106020640  GDF6; LOW QUALITY PROTEIN: growth/differentiation factor 6 [KO:K20012]
110351557  GDF7; growth/differentiation factor 7 [KO:K20013]
110352107  [KO:K19631]
113839982  INHBE; inhibin beta E chain [KO:K22689]
113840168  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
113842708  ID4; DNA-binding protein inhibitor ID-4 isoform X1 [KO:K17695]
113845281  [KO:K04658]
119713656  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
119713770  [KO:K04501]
119713790  [KO:K04677]
119713791  HJV; hemojuvelin [KO:K23100]
119714373  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
119715822  [KO:K13596] [EC:2.7.11.30]
119716123  [KO:K04674] [EC:2.7.11.30]
119717128  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
119717717  CHRD; chordin isoform X1 [KO:K04657]
119717892  [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
apla04010  MAPK signaling pathway
apla04110  Cell cycle
apla04120  Ubiquitin mediated proteolysis
apla04210  Apoptosis
KO pathway
ko04350   

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