KEGG   PATHWAY: rro04350
Entry
rro04350                    Pathway                                
Name
TGF-beta signaling pathway - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro04350  TGF-beta signaling pathway
rro04350

Other DBs
GO: 0007179
Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104653572  SKI; ski oncogene isoform X1 [KO:K26503]
104653653  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
104653723  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
104654123  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
104654252  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
104654271  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
104654770  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
104654879  BMP8B; bone morphogenetic protein 8B [KO:K16622]
104654915  [KO:K16622]
104655082  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
104655463  ROCK1; LOW QUALITY PROTEIN: rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
104655489  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
104655647  E2F4; transcription factor E2F4 [KO:K04682]
104655806  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
104656128  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
104657112  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
104657765  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
104657832  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
104657944  FBN1; fibrillin-1 isoform X2 [KO:K06825]
104659681  THBS1; thrombospondin-1 [KO:K16857]
104659781  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
104659809  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
104659810  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
104660000  SMAD7; mothers against decapentaplegic homolog 7 isoform X3 [KO:K19631]
104660801  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
104661913  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104661983  NODAL; nodal homolog [KO:K04666]
104662035  RGMB; RGM domain family member B [KO:K06847]
104662237  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
104662252  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
104662580  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
104662628  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
104662932  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
104663128  INHBA; inhibin beta A chain [KO:K04667]
104663544  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
104663612  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
104663775  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
104664085  IFNG; interferon gamma [KO:K04687]
104664619  CHRD; chordin isoform X1 [KO:K04657]
104664740  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
104665088  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
104666517  GREM1; gremlin-1 [KO:K23318]
104666573  EMP3; epithelial membrane protein 3 [KO:K26257]
104667014  CUL1; cullin-1 [KO:K03347]
104667111  HAMP; hepcidin [KO:K23106]
104667372  RHOA; transforming protein RhoA [KO:K04513]
104667855  IGSF1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
104668221  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104668671  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
104668728  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
104669133  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
104669157  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
104669332  SKIL; ski-like protein [KO:K18499]
104669442  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X11 [KO:K19559]
104670594  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
104670595  SP1; transcription factor Sp1 [KO:K04684]
104670653  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
104671038  HJV; hemojuvelin isoform X1 [KO:K23100]
104671369  [KO:K04683]
104671445  AMH; muellerian-inhibiting factor [KO:K04665]
104671563  GDF6; growth/differentiation factor 6 [KO:K20012]
104672074  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
104672289  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
104672474  FST; follistatin isoform X1 [KO:K04661]
104672615  INHBB; inhibin beta B chain [KO:K22687]
104672685  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
104672916  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
104673260  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104673417  [KO:K19383]
104673455  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
104673622  TFR2; transferrin receptor protein 2 isoform X2 [KO:K23910]
104674485  FMOD; fibromodulin [KO:K08121]
104674798  MYC; myc proto-oncogene protein [KO:K04377]
104675057  [KO:K14736]
104675219  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
104675498  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
104675832  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
104675989  NOG; noggin [KO:K04658]
104676086  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
104676376  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
104676388  TFRC; transferrin receptor protein 1 [KO:K06503]
104676563  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
104676834  BMP6; bone morphogenetic protein 6 [KO:K16620]
104676866  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104676998  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
104677103  [KO:K04668]
104677224  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
104677263  [KO:K03094]
104677337  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
104677352  [KO:K06067] [EC:3.5.1.98]
104677599  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
104677898  GDF7; growth/differentiation factor 7 isoform X1 [KO:K20013]
104677938  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
104678067  NEO1; neogenin isoform X1 [KO:K06766]
104678612  DCN; decorin [KO:K04660]
104679198  GREM2; gremlin-2 [KO:K23318]
104679825  [KO:K19558]
104679852  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
104680178  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
104680529  GDF5; growth/differentiation factor 5 [KO:K04664]
104680550  TGIF2; homeobox protein TGIF2 [KO:K19553]
104680809  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104681440  NCOR1; nuclear receptor corepressor 1 isoform X7 [KO:K04650]
104681477  BMP2; bone morphogenetic protein 2 [KO:K21283]
104681595  BMP5; bone morphogenetic protein 5 [KO:K04663]
104682365  INHBE; inhibin beta E chain [KO:K22689]
104682366  INHBC; inhibin beta C chain [KO:K22688]
104682426  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
115892000  [KO:K04683]
115894564  [KO:K04683]
115895835  [KO:K04683]
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
rro04010  MAPK signaling pathway
rro04110  Cell cycle
rro04120  Ubiquitin mediated proteolysis
rro04210  Apoptosis
KO pathway
ko04350   

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