KEGG   PATHWAY: cfa04350
Entry
cfa04350                    Pathway                                
Name
TGF-beta signaling pathway - Canis lupus familiaris (dog)
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
cfa04350  TGF-beta signaling pathway
cfa04350

Other DBs
GO: 0007179
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
100683515  NOG; noggin [KO:K04658]
100684945  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100686903  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100688951  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
100855618  [KO:K16622]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100856151  RGMA; repulsive guidance molecule A isoform X2 [KO:K23096]
100856447  INHBE; inhibin beta E chain isoform X1 [KO:K22689]
102151783  [KO:K17693]
102152821  GDF7; LOW QUALITY PROTEIN: growth/differentiation factor 7 [KO:K20013]
102155562  [KO:K19553]
106558270  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
111090648  [KO:K03094]
119870005  [KO:K22687]
403547  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
403608  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
403703  TFRC; transferrin receptor protein 1 [KO:K06503]
403801  IFNG; interferon gamma precursor [KO:K04687]
403904  DCN; decorin precursor [KO:K04660]
403922  TNF; tumor necrosis factor [KO:K03156]
403924  MYC; myc proto-oncogene protein [KO:K04377]
403954  RHOA; transforming protein RhoA [KO:K04513]
403998  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
474494  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X2 [KO:K03868] [EC:2.3.2.32]
474682  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
474944  BMP5; bone morphogenetic protein 5 [KO:K04663]
475035  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
475352  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X8 [KO:K04679]
475456  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
475512  CUL1; cullin-1 [KO:K03347]
475720  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X4 [KO:K19559]
475830  HJV; hemojuvelin isoform X2 [KO:K23100]
476140  ACVR2A; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
476196  SMAD4; mothers against decapentaplegic homolog 4 isoform X2 [KO:K04501]
477039  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
477071  [KO:K14736]
477072  [KO:K14736]
477162  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
477221  RBL1; retinoblastoma-like protein 1 isoform X3 [KO:K04681]
477270  BMP7; bone morphogenetic protein 7 precursor [KO:K16621]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
478293  FBN1; fibrillin-1 precursor [KO:K06825]
478372  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
478484  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
478715  BMP6; LOW QUALITY PROTEIN: bone morphogenetic protein 6 [KO:K16620]
478757  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
478875  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
479146  RGMB; RGM domain family member B [KO:K06847]
479167  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
479336  FST; follistatin isoform X1 [KO:K04661]
479444  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
479515  NCOR1; nuclear receptor corepressor 1 isoform X10 [KO:K04650]
479866  CREBBP; CREB-binding protein isoform X8 [KO:K04498] [EC:2.3.1.48]
480144  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
480181  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
480470  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
480580  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X3 [KO:K04688] [EC:2.7.11.1]
481051  IGSF1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
481520  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
481563  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
481628  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
482522  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
482873  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
483245  INHBA; inhibin beta A chain [KO:K04667]
483880  INHBB; inhibin beta B chain [KO:K22687]
484335  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
484408  EMP3; epithelial membrane protein 3 [KO:K26257]
485072  AMH; muellerian-inhibiting factor precursor [KO:K04665]
485180  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
485590  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
485850  GDF5; growth/differentiation factor 5 [KO:K04664]
485857  TGIF2; homeobox protein TGIF2 [KO:K19553]
486006  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
486506  AMHR2; LOW QUALITY PROTEIN: anti-Muellerian hormone type-2 receptor isoform X5 [KO:K04672] [EC:2.7.11.30]
486507  SP1; transcription factor Sp1 isoform X2 [KO:K04684]
486537  ACVR1B; activin receptor type-1B isoform X3 [KO:K13567] [EC:2.7.11.30]
487081  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
487309  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
487403  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X2 [KO:K19558]
487475  GREM1; gremlin-1 [KO:K23318]
487486  THBS1; thrombospondin-1 [KO:K16857]
487612  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
487628  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X2 [KO:K23377]
487635  NEO1; neogenin isoform X20 [KO:K06766]
487902  PITX2; pituitary homeobox 2 isoform X2 [KO:K04686]
488032  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
488159  SKIL; ski-like protein isoform X1 [KO:K18499]
488361  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
488560  FMOD; fibromodulin [KO:K08121]
488596  TGFB2; transforming growth factor beta-2 proprotein isoform X3 [KO:K13376]
489028  NODAL; nodal homolog isoform X1 [KO:K04666]
489077  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
489610  SKI; ski oncogene isoform X7 [KO:K26503]
489834  TFR2; transferrin receptor protein 2 [KO:K23910]
490367  GREM2; gremlin-2 isoform X2 [KO:K23318]
490387  [KO:K04668]
490537  TGIF1; homeobox protein TGIF1 [KO:K19383]
490570  SMAD7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
490695  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
490796  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
492281  HAMP; hepcidin precursor [KO:K23106]
607289  CHRD; chordin isoform X4 [KO:K04657]
607422  INHBC; inhibin beta C chain [KO:K22688]
607720  TFDP1; transcription factor Dp-1 [KO:K04683]
607768  [KO:K16622]
608380  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
608821  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
609779  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
610499  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X2 [KO:K04688] [EC:2.7.11.1]
610902  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
611103  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
611243  E2F4; transcription factor E2F4 [KO:K04682]
611909  LEFTY1; left-right determination factor 1 isoform X2 [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
cfa04010  MAPK signaling pathway
cfa04110  Cell cycle
cfa04120  Ubiquitin mediated proteolysis
cfa04210  Apoptosis
KO pathway
ko04350   

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