KEGG   PATHWAY: ccay04350
Entry
ccay04350                   Pathway                                
Name
TGF-beta signaling pathway - Caretta caretta (Loggerhead turtle)
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
ccay04350  TGF-beta signaling pathway
ccay04350

Other DBs
GO: 0007179
Organism
Caretta caretta (Loggerhead turtle) [GN:ccay]
Gene
125643191  CHRD; LOW QUALITY PROTEIN: chordin [KO:K04657]
125621199  NOG; noggin [KO:K04658]
125644435  noggin-2-like [KO:K04658]
125624540  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
125633858  GREM2; gremlin-2 [KO:K23318]
125638884  GREM1; gremlin-1 [KO:K23318]
125638126  THBS1; thrombospondin-1 [KO:K16857]
125630106  DCN; decorin [KO:K04660]
125625194  FMOD; fibromodulin [KO:K08121]
125634950  left-right determination factor 2-like [KO:K04668]
125636623  FST; follistatin isoform X1 [KO:K04661]
125639796  bone morphogenetic protein 2-like [KO:K21283]
125633370  BMP2; bone morphogenetic protein 2 [KO:K21283]
125627346  bone morphogenetic protein 2-like [KO:K21283]
125638901  BMP4; bone morphogenetic protein 4 [KO:K04662]
125632120  BMP6; bone morphogenetic protein 6 [KO:K16620]
125644974  INHBB; inhibin beta B chain [KO:K22687]
125642807  ovotransferrin-like [KO:K14736]
125634464  BMP5; bone morphogenetic protein 5 [KO:K04663]
125622393  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
125624656  bone morphogenetic protein 8A-like [KO:K16622]
125622216  GDF5; growth/differentiation factor 5 [KO:K04664]
125632690  GDF6; growth/differentiation factor 6 [KO:K20012]
125634617  GDF7; growth/differentiation factor 7 [KO:K20013]
125627141  AMH; muellerian-inhibiting factor [KO:K04665]
125630233  IFNG; interferon gamma [KO:K04687]
125621230  tumor necrosis factor-like [KO:K03156]
125621277  LOW QUALITY PROTEIN: tumor necrosis factor-like [KO:K03156]
125643850  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
125644191  FBN1; fibrillin-1 isoform X1 [KO:K06825]
125633802  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
125628071  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
125633641  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
125639078  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
125631833  INHBA; inhibin beta A chain [KO:K04667]
125627751  inhibin beta C chain-like [KO:K22688]
125627759  inhibin beta C chain-like [KO:K22688]
125629274  LOW QUALITY PROTEIN: inhibin beta C chain-like [KO:K22688]
125626329  NODAL; nodal homolog [KO:K04666]
125639511  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
125635348  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
125645172  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
125645134  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
125626022  HJV; hemojuvelin [KO:K23100]
125643481  NEO1; neogenin isoform X1 [KO:K06766]
125628561  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
125642602  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
125626999  repulsive guidance molecule A-like [KO:K23096]
125643986  RGMA; repulsive guidance molecule A [KO:K23096]
125636748  RGMB; repulsive guidance molecule B [KO:K06847]
125627417  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
125631915  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
125631639  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
125645204  LOW QUALITY PROTEIN: TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
125627996  EMP3; LOW QUALITY PROTEIN: epithelial membrane protein 3 [KO:K26257]
125642366  transforming growth factor beta activator LRRC32-like [KO:K26316]
125632246  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
125643072  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
125627547  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
125631207  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
125631308  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
125635603  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
125641297  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
125635862  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
125636648  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
125643757  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
125636758  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
125625862  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4-like [KO:K04501]
125644038  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
125625933  mothers against decapentaplegic homolog 6-like [KO:K04677]
125637068  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
125621068  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
125643657  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
125641235  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
125637444  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
125629578  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
125641621  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
125623233  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
125638210  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125639525  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
125628424  transforming protein RhoA-like isoform X1 [KO:K04513]
125632360  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
125625662  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
125641617  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
125636215  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
125624078  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
125639172  RPS6KB2; LOW QUALITY PROTEIN: ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
125626059  hepcidin [KO:K23106]
125625864  hepcidin-like [KO:K23106]
125622403  ID1; DNA-binding protein inhibitor ID-1 isoform X1 [KO:K04680]
125634545  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
125624791  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
125632191  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
125622408  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
125632614  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
125645299  E2F4; transcription factor E2F4 [KO:K04682]
125639293  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
125629580  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
125644386  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
125627418  SP1; transcription factor Sp1 [KO:K04684]
125642574  SKIL; ski-like protein [KO:K18499]
125624298  SKI; ski oncogene isoform X1 [KO:K26503]
125643510  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
125634259  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
125624685  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
125623766  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
125632339  TGIF1; homeobox protein TGIF1 [KO:K19383]
125622410  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
125632839  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
125636630  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
125636631  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
125635780  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
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
Related
pathway
ccay04010  MAPK signaling pathway
ccay04110  Cell cycle
ccay04120  Ubiquitin mediated proteolysis
ccay04210  Apoptosis
KO pathway
ko04350   
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