KEGG   PATHWAY: cge04350
Entry
cge04350                    Pathway                                
Name
TGF-beta signaling pathway - Cricetulus griseus (Chinese hamster)
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
cge04350  TGF-beta signaling pathway
cge04350

Other DBs
GO: 0007179
Organism
Cricetulus griseus (Chinese hamster) [GN:cge]
Gene
100774612  Chrd; chordin isoform X4 [KO:K04657]
100764827  Nog; noggin isoform X2 [KO:K04658]
100752634  Nbl1; neuroblastoma suppressor of tumorigenicity 1 isoform X2 [KO:K19558]
100758320  Grem1; gremlin-1 isoform X1 [KO:K23318]
100773984  Grem2; gremlin-2 [KO:K23318]
100760878  Thbs1; thrombospondin-1 isoform X1 [KO:K16857]
100756152  Dcn; decorin [KO:K04660]
100765932  Fmod; fibromodulin [KO:K08121]
100751377  left-right determination factor 1 [KO:K04668]
100751951  left-right determination factor 2 isoform X1 [KO:K04668]
100774874  Fst; follistatin isoform X4 [KO:K04661]
100752564  Bmp2; bone morphogenetic protein 2 isoform X2 [KO:K21283]
100754303  Bmp4; bone morphogenetic protein 4 [KO:K04662]
100768517  Bmp6; bone morphogenetic protein 6 isoform X1 [KO:K16620]
100759312  Inhbb; LOW QUALITY PROTEIN: inhibin beta B chain isoform X2 [KO:K22687]
100761626  inhibitor of carbonic anhydrase [KO:K14736]
100767241  serotransferrin [KO:K14736]
100763439  Bmp5; bone morphogenetic protein 5 [KO:K04663]
100759897  Bmp7; bone morphogenetic protein 7 [KO:K16621]
100773147  bone morphogenetic protein 8B [KO:K16622]
100771494  Bmp8a; bone morphogenetic protein 8A [KO:K16622]
100762027  growth/differentiation factor 5 isoform X2 [KO:K04664]
113834414  growth/differentiation factor 6 [KO:K20012]
113836599  growth/differentiation factor 7-like isoform X1 [KO:K20013]
100759997  Amh; muellerian-inhibiting factor isoform X2 [KO:K04665]
100768486  Ifng; interferon gamma isoform X2 [KO:K04687]
100764780  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
100752597  Thsd4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
100761283  Fbn1; fibrillin-1 isoform X2 [KO:K06825]
100764759  Ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X6 [KO:K19559]
100773359  Tgfb1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
100774918  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
100756831  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
100762446  Inhba; inhibin beta A chain [KO:K04667]
100755878  Inhbc; inhibin beta C chain [KO:K22688]
100756167  Inhbe; inhibin beta E chain [KO:K22689]
100762314  Nodal; nodal homolog [KO:K04666]
100750332  Bmpr1a; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100774629  bone morphogenetic protein receptor type-1B isoform X4 [KO:K13578] [EC:2.7.11.30]
100758565  Acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
100764519  Bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100774605  Acvr2a; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
100756322  hemojuvelin [KO:K23100]
100759045  Neo1; neogenin isoform X2 [KO:K06766]
100762132  Hfe; hereditary hemochromatosis protein isoform X2 [KO:K26535]
100752766  Tfr2; transferrin receptor protein 2 [KO:K23910]
100689395  Tfrc; transferrin receptor protein 1 [KO:K06503]
100758121  Rgma; repulsive guidance molecule A isoform X2 [KO:K23096]
100753047  Rgmb; RGM domain family member B isoform X2 [KO:K06847]
100772657  Amhr2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
100772727  Tgfbr1; TGF-beta receptor type-1 isoform X3 [KO:K04674] [EC:2.7.11.30]
100773953  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100751496  Emp3; epithelial membrane protein 3 isoform X2 [KO:K26257]
100774110  transforming growth factor beta activator LRRC32 [KO:K26316]
100752267  Nrros; transforming growth factor beta activator LRRC33 [KO:K26317]
100764812  Acvr1b; activin receptor type-1B isoform X3 [KO:K13567] [EC:2.7.11.30]
100755103  Acvr2b; activin receptor type-2B isoform X5 [KO:K13596] [EC:2.7.11.30]
100756930  Acvr1c; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
100768646  Igsf1; immunoglobulin superfamily member 1 isoform X10 [KO:K26168]
100771599  Bambi; BMP and activin membrane-bound inhibitor homolog isoform X2 [KO:K10162]
100768619  Smad1; mothers against decapentaplegic homolog 1 isoform X2 [KO:K04676]
100756412  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1 isoform X2 [KO:K04676]
113838231  mothers against decapentaplegic homolog 1-like isoform X3 [KO:K04676]
113838959  mothers against decapentaplegic homolog 1-like isoform X1 [KO:K04676]
113839037  mothers against decapentaplegic homolog 1-like [KO:K04676]
113839048  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113839010  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838058  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838575  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838576  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838579  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113830739  mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
113838585  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838617  mothers against decapentaplegic homolog 1-like isoform X1 [KO:K04676]
100774946  mothers against decapentaplegic homolog 1 isoform X2 [KO:K04676]
113837974  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838618  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838655  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838723  mothers against decapentaplegic homolog 1-like isoform X1 [KO:K04676]
113838725  mothers against decapentaplegic homolog 1-like isoform X3 [KO:K04676]
113838868  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838875  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838915  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838760  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838795  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838826  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838851  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113838332  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113830754  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838333  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838335  mothers against decapentaplegic homolog 1-like isoform X1 [KO:K04676]
113839093  mothers against decapentaplegic homolog 1-like isoform X3 [KO:K04676]
113838325  mothers against decapentaplegic homolog 1-like isoform X2 [KO:K04676]
113838327  mothers against decapentaplegic homolog 1-like [KO:K04676]
113839150  mothers against decapentaplegic homolog 1-like [KO:K04676]
113837941  mothers against decapentaplegic homolog 1-like [KO:K04676]
113838323  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
113839079  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
118239754  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
118239765  LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 1-like [KO:K04676]
100754116  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
100766405  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
100771578  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100759220  Smad3; mothers against decapentaplegic homolog 3 isoform X3 [KO:K23605]
100770737  Smad4; mothers against decapentaplegic homolog 4 isoform X2 [KO:K04501]
100758934  Smad6; mothers against decapentaplegic homolog 6 isoform X2 [KO:K04677]
100766709  Smad7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
100765164  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X2 [KO:K04678] [EC:2.3.2.26]
100773704  Smurf2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
100754284  Zfyve9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
100761003  Zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
100762556  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100757763  Cul1; cullin-1 [KO:K03347]
100757677  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
100759514  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100753149  Mapk3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
100762797  Rhoa; transforming protein RhoA [KO:K04513]
100757042  transforming protein RhoA isoform X1 [KO:K04513]
100770074  Rock1; rho-associated protein kinase 1 isoform X3 [KO:K04514] [EC:2.7.11.1]
100771272  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
100773447  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
100757400  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X2 [KO:K04382] [EC:3.1.3.16]
103164195  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X2 [KO:K04382] [EC:3.1.3.16]
118237628  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X2 [KO:K04382] [EC:3.1.3.16]
100757513  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100760227  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
100757672  hepcidin [KO:K23106]
100774183  Id1; DNA-binding protein inhibitor ID-1 isoform X1 [KO:K04680]
100769110  Id2; DNA-binding protein inhibitor ID-2 isoform X1 [KO:K17693]
100751577  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
113835065  DNA-binding protein inhibitor ID-4 [KO:K17695]
100755818  Rbl1; retinoblastoma-like protein 1 isoform X2 [KO:K04681]
103160151  E2f5; transcription factor E2F5 [KO:K04682]
100765561  E2f4; transcription factor E2F4 isoform X3 [KO:K04682]
100774706  Tfdp1; transcription factor Dp-1 isoform X4 [KO:K04683]
100762260  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100770451  histone lysine acetyltransferase CREBBP isoform X3 [KO:K04498] [EC:2.3.1.48]
100767199  Sp1; transcription factor Sp1 isoform X3 [KO:K04684]
100765342  Skil; ski-like protein isoform X1 [KO:K18499]
100755403  Ski; ski oncogene isoform X2 [KO:K26503]
100761538  Sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
100764557  Hdac2; histone deacetylase 2 isoform X2 [KO:K06067] [EC:3.5.1.98]
100752721  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100761556  histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
100760832  Ncor1; nuclear receptor corepressor 1 isoform X2 [KO:K04650]
100774130  Tgif1; homeobox protein TGIF1 isoform X1 [KO:K19383]
100753778  Tgif2; homeobox protein TGIF2 [KO:K19553]
100773301  Myc; myc proto-oncogene protein isoform X2 [KO:K04377]
113833995  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100755816  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
cge04010  MAPK signaling pathway
cge04110  Cell cycle
cge04120  Ubiquitin mediated proteolysis
cge04210  Apoptosis
KO pathway
ko04350   
LinkDB

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