KEGG   PATHWAY: gas04350
Entry
gas04350                    Pathway                                
Name
TGF-beta signaling pathway - Gracilinanus agilis (agile gracile opossum)
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
gas04350  TGF-beta signaling pathway
gas04350

Other DBs
GO: 0007179
Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123230857  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123231024  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
123231247  [KO:K04685]
123231248  [KO:K04685]
123231381  RGMB; repulsive guidance molecule B isoform X1 [KO:K06847]
123231726  [KO:K04498] [EC:2.3.1.48]
123231757  TGIF1; homeobox protein TGIF1 [KO:K19383]
123231825  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
123231898  GDF6; growth/differentiation factor 6 [KO:K20012]
123233560  BMP7; bone morphogenetic protein 7 [KO:K16621]
123234107  FBN1; fibrillin-1 [KO:K06825]
123234204  RGMA; repulsive guidance molecule A [KO:K23096]
123234308  [KO:K21283]
123234357  NEO1; neogenin [KO:K06766]
123234379  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
123234651  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
123234746  BMP2; bone morphogenetic protein 2 [KO:K21283]
123234940  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
123235417  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
123235711  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
123235744  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
123235751  BMP4; bone morphogenetic protein 4 [KO:K04662]
123235863  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123235983  GREM1; gremlin-1 isoform X1 [KO:K23318]
123236435  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
123236506  NODAL; nodal homolog [KO:K04666]
123236581  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
123237051  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
123237411  RBL1; retinoblastoma-like protein 1 [KO:K04681]
123237427  TGIF2; homeobox protein TGIF2 [KO:K19553]
123237637  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123237642  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
123237705  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
123237729  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
123237869  [KO:K04513]
123237918  THBS1; thrombospondin-1 [KO:K16857]
123238024  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
123238038  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
123238039  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
123238314  E2F5; transcription factor E2F5 [KO:K04682]
123238783  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
123238845  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
123239364  INHBB; inhibin beta B chain [KO:K22687]
123239370  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
123239438  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
123239919  EMP3; epithelial membrane protein 3 [KO:K26257]
123240302  SKIL; ski-like protein [KO:K18499]
123240342  BMP6; bone morphogenetic protein 6 [KO:K16620]
123240434  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
123240795  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123240843  [KO:K26168]
123240933  SKI; ski oncogene [KO:K26503]
123241543  MYC; myc proto-oncogene protein [KO:K04377]
123241835  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
123242250  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
123242271  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
123242337  TFRC; transferrin receptor protein 1 [KO:K06503]
123242608  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
123242702  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
123242809  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
123243020  [KO:K23106]
123243117  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
123243140  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
123243249  BMP8A; bone morphogenetic protein 8A [KO:K16622]
123243587  [KO:K04668]
123243849  AMH; muellerian-inhibiting factor [KO:K04665]
123243924  FMOD; fibromodulin [KO:K08121]
123244235  HJV; hemojuvelin isoform X1 [KO:K23100]
123244498  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
123244843  TFR2; transferrin receptor protein 2 [KO:K23910]
123245100  TNF; tumor necrosis factor [KO:K03156]
123245378  [KO:K16790]
123245533  GREM2; gremlin-2 [KO:K23318]
123245714  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
123245809  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
123245982  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
123246232  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
123246290  HFE; hereditary hemochromatosis protein [KO:K26535]
123246498  INHBA; inhibin beta A chain [KO:K04667]
123247109  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
123247757  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
123247856  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
123247923  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
123248635  INHBC; inhibin beta C chain [KO:K22688]
123248649  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
123248986  DCN; decorin [KO:K04660]
123249047  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
123249464  RHOA; transforming protein RhoA [KO:K04513]
123249621  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
123249659  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
123249675  CUL1; cullin-1 [KO:K03347]
123249688  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123250180  IFNG; interferon gamma [KO:K04687]
123250221  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
123250301  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
123250447  SP1; transcription factor Sp1 [KO:K04684]
123250747  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
123251011  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123251607  PITX2; pituitary homeobox 2 [KO:K04686]
123251850  FST; follistatin [KO:K04661]
123251954  [KO:K04514] [EC:2.7.11.39]
123251960  [KO:K03094]
123252087  [KO:K04514] [EC:2.7.11.39]
123252361  [KO:K04382] [EC:3.1.3.16]
123252917  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
123252994  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
123253139  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
123253712  [KO:K26316]
123253784  [KO:K04501]
123254166  INHBE; inhibin beta E chain [KO:K22689]
123254358  [KO:K04501]
123255348  [KO:K04657]
123255477  NOG; noggin [KO:K04658]
123256028  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123256336  [KO:K06067] [EC:3.5.1.98]
123256692  GDF5; growth/differentiation factor 5 [KO:K04664]
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
gas04010  MAPK signaling pathway
gas04110  Cell cycle
gas04120  Ubiquitin mediated proteolysis
gas04210  Apoptosis
KO pathway
ko04350   

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