KEGG   PATHWAY: gja04350
Entry
gja04350                    Pathway                                
Name
TGF-beta signaling pathway - Gekko japonicus (Schlegel's Japanese gecko)
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
gja04350  TGF-beta signaling pathway
gja04350

Other DBs
GO: 0007179
Organism
Gekko japonicus (Schlegel's Japanese gecko) [GN:gja]
Gene
107123570  CHRD; chordin [KO:K04657]
107106666  NOG; noggin [KO:K04658]
107105668  nog2; noggin-2-like [KO:K04658]
107119423  GREM2; gremlin 2, DAN family BMP antagonist [KO:K23318]
107121239  GREM1; gremlin 1, DAN family BMP antagonist [KO:K23318]
107119648  THBS1; thrombospondin 1 [KO:K16857]
107113941  DCN; decorin [KO:K04660]
107107081  FMOD; fibromodulin [KO:K08121]
107125545  left-right determination factor 2-like [KO:K04668]
107117112  FST; follistatin [KO:K04661]
107105603  bone morphogenetic protein 2-like [KO:K21283]
107118716  bone morphogenetic protein 2-like [KO:K21283]
107123913  BMP2; bone morphogenetic protein 2 [KO:K21283]
107118494  BMP4; bone morphogenetic protein 4 [KO:K04662]
107121262  BMP6; bone morphogenetic protein 6 [KO:K16620]
107108952  INHBB; inhibin beta B subunit [KO:K22687]
107113976  ovotransferrin-like [KO:K14736]
107107933  BMP5; bone morphogenetic protein 5 [KO:K04663]
107119897  BMP7; bone morphogenetic protein 7 [KO:K16621]
107115951  bone morphogenetic protein 8B-like [KO:K16622]
107107860  GDF5; growth differentiation factor 5 [KO:K04664]
107109246  GDF6; growth differentiation factor 6 [KO:K20012]
107109455  GDF7; growth differentiation factor 7 [KO:K20013]
107122038  AMH; anti-Mullerian hormone [KO:K04665]
107105706  interferon gamma-like [KO:K04687]
107119827  tumor necrosis factor-like [KO:K03156]
107110346  thrombospondin type-1 domain-containing protein 4-like [KO:K23377]
107110932  FBN1; fibrillin 1 [KO:K06825]
107113457  latent-transforming growth factor beta-binding protein 1-like [KO:K19559]
107123911  TGFB1; transforming growth factor beta 1 [KO:K13375]
107110247  TGFB2; transforming growth factor beta 2 [KO:K13376]
107115203  transforming growth factor beta-2-like [KO:K13376]
107116455  TGFB3; transforming growth factor beta 3 [KO:K13377]
107116048  INHBA; inhibin beta A subunit [KO:K04667]
107108164  nodal homolog 2-A-like [KO:K04666]
107119743  NODAL; nodal growth differentiation factor [KO:K04666]
107122540  BMPR1A; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
107116711  BMPR1B; bone morphogenetic protein receptor type 1B [KO:K13578] [EC:2.7.11.30]
107110765  ACVR1; activin A receptor type 1 [KO:K04675] [EC:2.7.11.30]
107113314  BMPR2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
107108802  ACVR2A; activin A receptor type 2A [KO:K04670] [EC:2.7.11.30]
107113261  hemojuvelin-like [KO:K23100]
107111135  hemojuvelin-like [KO:K23100]
107122559  NEO1; neogenin 1 [KO:K06766]
107118078  TFR2; transferrin receptor 2 [KO:K23910]
107122245  TFRC; transferrin receptor [KO:K06503]
107113199  RGMA; repulsive guidance molecule family member a [KO:K23096]
107110504  RGM domain family member B-like [KO:K23096]
107113422  RGMB; repulsive guidance molecule family member b [KO:K06847]
107119662  AMHR2; anti-Mullerian hormone receptor type 2 [KO:K04672] [EC:2.7.11.30]
107109116  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
107125583  TGF-beta receptor type-2-like [KO:K04388] [EC:2.7.11.30]
107125145  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107113134  EMP3; epithelial membrane protein 3 [KO:K26257]
107108427  LRRC32; leucine rich repeat containing 32 [KO:K26316]
107113974  NRROS; negative regulator of reactive oxygen species [KO:K26317]
107108994  ACVR1B; activin A receptor type 1B [KO:K13567] [EC:2.7.11.30]
107120367  ACVR2B; activin A receptor type 2B [KO:K13596] [EC:2.7.11.30]
107110745  ACVR1C; activin A receptor type 1C [KO:K13568] [EC:2.7.11.30]
107118992  BAMBI; BMP and activin membrane bound inhibitor [KO:K10162]
107120265  SMAD1; SMAD family member 1 [KO:K04676]
107114480  SMAD5; SMAD family member 5 [KO:K16790]
107106042  SMAD9; SMAD family member 9 [KO:K16791]
107118628  SMAD2; SMAD family member 2 [KO:K04500]
107105564  SMAD3; SMAD family member 3 [KO:K23605]
107110886  mothers against decapentaplegic homolog 4-like [KO:K04501]
107122009  SMAD4; SMAD family member 4 [KO:K04501]
107124831  SMAD6; SMAD family member 6 [KO:K04677]
107117073  mothers against decapentaplegic homolog 6-like [KO:K04677]
107111185  SMAD7; SMAD family member 7 [KO:K19631]
107113584  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
107120879  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
107112774  zinc finger FYVE domain-containing protein 16-like [KO:K04679]
107111065  ZFYVE9; zinc finger FYVE-type containing 9 [KO:K04679]
107117140  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
107119625  CUL1; cullin 1 [KO:K03347]
107125984  SKP1; S-phase kinase associated protein 1 [KO:K03094]
107117455  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107115252  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107124777  transforming protein RhoA-like [KO:K04513]
107106083  transforming protein RhoA-like [KO:K04513]
107107158  RHOA; ras homolog family member A [KO:K04513]
107120578  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
107124393  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
107125982  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
107110575  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107123110  ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
107121293  ribosomal protein S6 kinase beta-2-like [KO:K04688] [EC:2.7.11.1]
107107186  ID2; inhibitor of DNA binding 2, HLH protein [KO:K17693]
107109579  ID3; inhibitor of DNA binding 3, HLH protein [KO:K17694]
107116368  ID4; inhibitor of DNA binding 4, HLH protein [KO:K17695]
107122224  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
107118852  E2F4; E2F transcription factor 4 [KO:K04682]
107122380  E2F5; E2F transcription factor 5 [KO:K04682]
107110920  TFDP1; transcription factor Dp-1 [KO:K04683]
107109304  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
107117161  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
107119663  SP1; Sp1 transcription factor [KO:K04684]
107110786  SKIL; SKI like proto-oncogene [KO:K18499]
107110192  SKI; SKI proto-oncogene [KO:K26503]
107121782  SIN3A; SIN3 transcription regulator family member A [KO:K11644]
107107742  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
107121973  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
107119554  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
107118008  TGIF1; TGFB induced factor homeobox 1 [KO:K19383]
107112275  TGIF2; TGFB induced factor homeobox 2 [KO:K19553]
107122472  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
107124310  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
107124306  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
107112511  PITX2; paired like homeodomain 2 [KO:K04686]
107118469  pituitary homeobox 2-like [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
gja04010  MAPK signaling pathway
gja04110  Cell cycle
gja04120  Ubiquitin mediated proteolysis
gja04210  Apoptosis
KO pathway
ko04350   
LinkDB

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