KEGG   PATHWAY: tup04350
Entry
tup04350                    Pathway                                
Name
TGF-beta signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04350  TGF-beta signaling pathway
tup04350

Other DBs
GO: 0007179
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102468100  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102468175  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102468598  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
102468744  ACVR2B; activin A receptor type 2B [KO:K13596] [EC:2.7.11.30]
102469035  RGMB; repulsive guidance molecule family member b [KO:K06847]
102469552  BMP2; bone morphogenetic protein 2 [KO:K21283]
102469819  NBL1; neuroblastoma 1, DAN family BMP antagonist [KO:K19558]
102469952  SKI; SKI proto-oncogene [KO:K26503]
102470542  IFNG; interferon gamma [KO:K04687]
102471047  BMP6; bone morphogenetic protein 6 [KO:K16620]
102471138  GDF7; growth differentiation factor 7 [KO:K20013]
102471341  RGMA; repulsive guidance molecule family member a [KO:K23096]
102471406  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
102471617  TFDP1; transcription factor Dp-1 [KO:K04683]
102471973  ACVR1; activin A receptor type 1 [KO:K04675] [EC:2.7.11.30]
102472078  SKIL; SKI like proto-oncogene [KO:K18499]
102472483  SMAD5; SMAD family member 5 [KO:K16790]
102472808  TGIF1; TGFB induced factor homeobox 1 [KO:K19383]
102472860  BMPR2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
102473003  SP1; Sp1 transcription factor [KO:K04684]
102473158  SMAD3; SMAD family member 3 [KO:K23605]
102473319  NRROS; negative regulator of reactive oxygen species [KO:K26317]
102473459  HFE2; hemochromatosis type 2 (juvenile) [KO:K23100]
102473796  FST; follistatin [KO:K04661]
102473834  AMHR2; anti-Mullerian hormone receptor type 2 [KO:K04672] [EC:2.7.11.30]
102474042  CHRD; chordin [KO:K04657]
102474976  DCN; decorin [KO:K04660]
102475423  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102475760  HFE; hemochromatosis [KO:K26535]
102476097  HAMP; hepcidin antimicrobial peptide [KO:K23106]
102476700  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102477439  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102477638  INHBA; inhibin beta A subunit [KO:K04667]
102477806  FMOD; fibromodulin [KO:K08121]
102477990  LEMD3; LEM domain containing 3 [KO:K19410]
102478066  GREM2; gremlin 2, DAN family BMP antagonist [KO:K23318]
102478188  TF; transferrin [KO:K14736]
102478256  GDF6; growth differentiation factor 6 [KO:K20012]
102479161  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102479251  ID3; inhibitor of DNA binding 3, HLH protein [KO:K17694]
102479564  NODAL; nodal growth differentiation factor [KO:K04666]
102480756  TFRC; transferrin receptor [KO:K06503]
102480902  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102481136  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
102481901  SMAD7; SMAD family member 7 [KO:K19631]
102482592  ZFYVE16; zinc finger FYVE-type containing 16 [KO:K04679]
102482737  EMP3; epithelial membrane protein 3 [KO:K26257]
102482985  E2F4; E2F transcription factor 4 [KO:K04682]
102483055  BMPR1A; bone morphogenetic protein receptor type 1A [KO:K04673] [EC:2.7.11.30]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483646  SKP1; S-phase kinase associated protein 1 [KO:K03094]
102483983  TGIF2; TGFB induced factor homeobox 2 [KO:K19553]
102484236  GREM1; gremlin 1, DAN family BMP antagonist [KO:K23318]
102484644  TFR2; transferrin receptor 2 [KO:K23910]
102484800  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102485966  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102486196  NCOR1; nuclear receptor corepressor 1 [KO:K04650]
102486518  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102487039  RHOA; ras homolog family member A [KO:K04513]
102487569  SMAD6; SMAD family member 6 [KO:K04677]
102487950  [KO:K04382] [EC:3.1.3.16]
102488524  TGFB1; transforming growth factor beta 1 [KO:K13375]
102490297  ACVR1B; activin A receptor type 1B [KO:K13567] [EC:2.7.11.30]
102490384  LEFTY1; left-right determination factor 1 [KO:K04668]
102490843  PITX2; paired like homeodomain 2 [KO:K04686]
102490878  SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
102490927  BAMBI; BMP and activin membrane bound inhibitor [KO:K10162]
102491055  SMAD9; SMAD family member 9 [KO:K16791]
102491127  SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
102492308  NOG; noggin [KO:K04658]
102492355  SMAD1; SMAD family member 1 [KO:K04676]
102493152  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102494008  SMAD4; SMAD family member 4 [KO:K04501]
102494120  LEFTY2; left-right determination factor 1 [KO:K04668]
102495054  [KO:K06825]
102495762  AMH; anti-Mullerian hormone [KO:K04665]
102495801  [KO:K04685]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496689  ZFYVE9; zinc finger FYVE-type containing 9 [KO:K04679]
102496847  [KO:K13578] [EC:2.7.11.30]
102497029  TGFB3; transforming growth factor beta 3 [KO:K13377]
102497446  CUL1; cullin 1 [KO:K03347]
102497450  ACVR1C; activin A receptor type 1C [KO:K13568] [EC:2.7.11.30]
102497487  BMP4; bone morphogenetic protein 4 [KO:K04662]
102497602  THBS1; thrombospondin 1 [KO:K16857]
102497968  TMEM53; transmembrane protein 53 [KO:K28359]
102497973  TNF; tumor necrosis factor [KO:K03156]
102499226  ACVR2A; activin A receptor type 2A [KO:K04670] [EC:2.7.11.30]
102499336  NEO1; neogenin 1 [KO:K06766]
102499541  SMAD2; SMAD family member 2 [KO:K04500]
102499781  INHBB; inhibin beta B subunit [KO:K22687]
102499809  ID2; inhibitor of DNA binding 2, HLH protein [KO:K17693]
102500173  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102500294  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
102500312  LTBP1; latent transforming growth factor beta binding protein 1 [KO:K19559]
102500358  BMP7; bone morphogenetic protein 7 [KO:K16621]
102500482  TGFB2; transforming growth factor beta 2 [KO:K13376]
102500633  SIN3A; SIN3 transcription regulator family member A [KO:K11644]
102500872  E2F5; E2F transcription factor 5 [KO:K04682]
102501307  LRRC32; leucine rich repeat containing 32 [KO:K26316]
102501427  ID1; inhibitor of DNA binding 1, HLH protein [KO:K04680]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102502000  INHBE; inhibin beta E subunit [KO:K22689]
102502425  INHBC; inhibin beta C subunit [KO:K22688]
102503216  BMP5; bone morphogenetic protein 5 [KO:K04663]
102503291  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102503316  GDF5; growth differentiation factor 5 [KO:K04664]
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
Reference
  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
tup04010  MAPK signaling pathway
tup04110  Cell cycle
tup04120  Ubiquitin mediated proteolysis
tup04210  Apoptosis
KO pathway
ko04350   

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