KEGG   PATHWAY: ccae04350
Entry
ccae04350                   Pathway                                
Name
TGF-beta signaling pathway - Cyanistes caeruleus (blue tit)
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
ccae04350  TGF-beta signaling pathway
ccae04350

Other DBs
GO: 0007179
Organism
Cyanistes caeruleus (blue tit) [GN:ccae]
Gene
111922308  E2F5; transcription factor E2F5 [KO:K04682]
111922490  TFRC; transferrin receptor protein 1 [KO:K06503]
111922707  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
111922805  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
111923501  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
111923644  CUL1; cullin-1 isoform X1 [KO:K03347]
111923669  INHBA; inhibin beta A chain [KO:K04667]
111923709  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
111923936  BMP6; bone morphogenetic protein 6 [KO:K16620]
111923990  TGIF1; homeobox protein TGIF1 [KO:K19383]
111924101  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
111924950  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
111925128  MYC; myc proto-oncogene protein [KO:K04377]
111925449  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
111925667  LRRC32; LOW QUALITY PROTEIN: leucine-rich repeat-containing protein 32 [KO:K26316]
111925868  BMP5; bone morphogenetic protein 5 [KO:K04663]
111926059  GDF7; growth/differentiation factor 7 [KO:K20013]
111926211  TGFB2; transforming growth factor beta-2 [KO:K13376]
111926633  BMP2; bone morphogenetic protein 2 [KO:K21283]
111926836  GREM2; gremlin-2 [KO:K23318]
111926965  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
111927165  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
111928335  PITX2; pituitary homeobox 2 [KO:K04686]
111928597  [KO:K26316]
111928834  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
111928993  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
111929421  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
111929526  BMP4; bone morphogenetic protein 4 [KO:K04662]
111929961  TGFB3; transforming growth factor beta-3 [KO:K13377]
111930312  THBS1; thrombospondin-1 [KO:K16857]
111930325  GREM1; gremlin-1 [KO:K23318]
111931148  [KO:K21283]
111931579  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
111931751  INHBB; LOW QUALITY PROTEIN: inhibin beta B chain [KO:K22687]
111931997  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
111932269  [KO:K04388] [EC:2.7.11.30]
111932342  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
111932400  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
111932401  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
111933049  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
111933131  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
111933323  SKIL; ski-like protein [KO:K18499]
111933390  CHRD; chordin [KO:K04657]
111933527  DCN; decorin [KO:K04660]
111933646  TF; serotransferrin [KO:K14736]
111933725  NRROS; negative regulator of reactive oxygen species [KO:K26317]
111933858  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
111933913  NEO1; neogenin [KO:K06766]
111933962  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
111934024  RGMA; repulsive guidance molecule A [KO:K23096]
111934114  FBN1; fibrillin-1 isoform X1 [KO:K06825]
111934179  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
111934263  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
111934592  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
111934630  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
111934756  E2F4; transcription factor E2F4 [KO:K04682]
111935135  RHOA; transforming protein RhoA [KO:K04513]
111935587  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
111935602  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
111935605  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
111936247  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
111936534  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111937200  IFNG; interferon gamma [KO:K04687]
111937422  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
111937795  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
111937833  RPS6KB1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
111938012  BMP7; bone morphogenetic protein 7 [KO:K16621]
111938353  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
111938374  GDF5; growth/differentiation factor 5 [KO:K04664]
111938521  [KO:K19558]
111938626  SKI; ski oncogene [KO:K26503]
111938967  [KO:K16622]
111939059  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
111939158  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
111939552  HJV; hemojuvelin [KO:K23100]
111939566  [KO:K04677]
111939778  FMOD; fibromodulin [KO:K08121]
111940221  AMH; muellerian-inhibiting factor [KO:K04665]
111940378  [KO:K21283]
111940460  SP1; transcription factor Sp1 [KO:K04684]
111940530  [KO:K22688]
111940581  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
111941053  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
111941079  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
111941128  [KO:K26316]
111941409  FST; follistatin [KO:K04661]
111941590  RGMB; RGM domain family member B [KO:K06847]
111941635  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
111942551  [KO:K13375]
111942682  [KO:K04382] [EC:3.1.3.16]
111942728  [KO:K08121]
111943811  NOG; noggin [KO:K04658]
111944867  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
111945072  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
111945593  [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
ccae04010  MAPK signaling pathway
ccae04110  Cell cycle
ccae04120  Ubiquitin mediated proteolysis
ccae04210  Apoptosis
KO pathway
ko04350   

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