KEGG   PATHWAY: rno04350
Entry
rno04350                    Pathway                                
Name
TGF-beta signaling pathway - Rattus norvegicus (rat)
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
rno04350  TGF-beta signaling pathway
rno04350

Other DBs
GO: 0007179
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100360427  E2f4; transcription factor E2F4 [KO:K04682]
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
114208  Skil; ski-like protein isoform 1 [KO:K18499]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116651  E2f5; transcription factor E2F5 [KO:K04682]
117273  Rhoa; transforming protein RhoA [KO:K04513]
117275  Chrd; chordin precursor [KO:K04657]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
140590  Bmpr2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
24373  Fst; follistatin precursor [KO:K04661]
24577  Myc; myc proto-oncogene protein [KO:K04377]
245921  Acvr1c; activin receptor type-1C precursor [KO:K13568] [EC:2.7.11.30]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
24790  Sp1; transcription factor Sp1 [KO:K04684]
24825  Tf; serotransferrin precursor [KO:K14736]
24835  Tnf; tumor necrosis factor [KO:K03156]
25164  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
25196  Inhbb; inhibin beta B chain precursor [KO:K22687]
25261  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
252833  Gdf7; growth/differentiation factor 7 isoform 2 precursor [KO:K20013]
252834  Gdf6; growth/differentiation factor 6 precursor [KO:K20012]
252835  Gdf5; growth/differentiation factor 5 preproprotein [KO:K04664]
25296  Bmp4; bone morphogenetic protein 4 precursor [KO:K04662]
25366  Acvr2b; activin receptor type-2B precursor [KO:K13596] [EC:2.7.11.30]
25378  Amh; muellerian-inhibiting factor precursor [KO:K04665]
25495  Nog; noggin precursor [KO:K04658]
25585  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
25587  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
25631  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
25644  Bmp6; bone morphogenetic protein 6 precursor [KO:K16620]
25671  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
25712  Ifng; interferon gamma precursor [KO:K04687]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
287280  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
288562  Tfr2; transferrin receptor protein 2 [KO:K23910]
289264  Grem2; gremlin-2 precursor [KO:K23318]
289316  Lefty2; left-right determination factor 2 precursor [KO:K04668]
291023  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
29139  Dcn; decorin precursor [KO:K04660]
29199  Hfe; hereditary hemochromatosis protein homolog isoform 1 precursor [KO:K26535]
29200  Inhba; inhibin beta A chain preproprotein [KO:K04667]
29263  Acvr2a; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
293135  Lrrc32; transforming growth factor beta activator LRRC32 precursor [KO:K26316]
29357  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
29373  Bmp2; bone morphogenetic protein 2 precursor [KO:K21283]
29381  Acvr1b; activin receptor type-1B precursor [KO:K13567] [EC:2.7.11.30]
294503  Nodal; nodal homolog precursor [KO:K04666]
29530  Amhr2; anti-Muellerian hormone type-2 receptor precursor [KO:K04672] [EC:2.7.11.30]
29591  Tgfbr1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
297893  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
300084  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
302822  Igsf1; immunoglobulin superfamily member 1 precursor [KO:K26168]
303614  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
303875  Nrros; transforming growth factor beta activator LRRC33 precursor [KO:K26317]
308739  Rgma; repulsive guidance molecule A [KO:K23096]
310681  Hjv; hemojuvelin precursor [KO:K23100]
310914  Bmpr1b; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
313477  Zfyve9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
313529  Tmem53; transmembrane protein 53 [KO:K28359]
313757  Ski; ski oncogene isoform X1 [KO:K26503]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
315728  Thsd4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
315824  Bmp5; bone morphogenetic protein 5 precursor [KO:K04663]
315963  Inhca; Inhibitor of carbonic anhydrase precursor [KO:K14736]
316742  Tgif1; homeobox protein TGIF1 [KO:K19383]
361178  Tfdp1; transcription factor Dp-1 [KO:K04683]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
362356  Cul1; cullin-1 [KO:K03347]
363067  Sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
367100  Smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
445442  Thbs1; thrombospondin-1 isoform 1 precursor [KO:K16857]
498299  Lefty1; left-right determination factor 1 precursor [KO:K04668]
499508  Zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
499929  Tgif2; homeobox protein TGIF2 [KO:K19553]
50554  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
50566  Grem1; gremlin-1 precursor [KO:K23318]
50594  Nbl1; neuroblastoma suppressor of tumorigenicity 1 precursor [KO:K19558]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
54284  Pitx2; pituitary homeobox 2 isoform 1 [KO:K04686]
54299  Ncor1; nuclear receptor corepressor 1 [KO:K04650]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
59107  Ltbp1; latent-transforming growth factor beta-binding protein 1 precursor [KO:K19559]
59328  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
64507  Fmod; fibromodulin precursor [KO:K08121]
64549  Inhbc; inhibin beta C chain precursor [KO:K22688]
64678  Tfrc; transferrin receptor protein 1 [KO:K06503]
679119  Bmp8b; bone morphogenetic protein 8B isoform X2 [KO:K16622]
680066  Lemd3; inner nuclear membrane protein Man1 [KO:K19410]
680111  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
680931  Bmp8a; bone morphogenetic protein 8A precursor [KO:K16622]
681433  Rgmb; repulsive guidance molecule B [KO:K06847]
690516  Smurf1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
79558  Acvr1; activin receptor type-1 precursor [KO:K04675] [EC:2.7.11.30]
81505  Emp3; epithelial membrane protein 3 [KO:K26257]
81507  Bmpr1a; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
81516  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
81735  Neo1; neogenin precursor [KO:K06766]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
81810  Tgfbr2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
83711  Inhbe; inhibin beta E chain precursor [KO:K22689]
83727  Fbn1; fibrillin-1 precursor [KO:K06825]
83837  Bambi; BMP and activin membrane-bound inhibitor homolog precursor [KO:K10162]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
84576  Hdac1l; histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
84577  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
84604  Hamp; hepcidin precursor [KO:K23106]
85272  Bmp7; bone morphogenetic protein 7 precursor [KO:K16621]
85435  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
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
rno04010  MAPK signaling pathway
rno04110  Cell cycle
rno04120  Ubiquitin mediated proteolysis
rno04210  Apoptosis
KO pathway
ko04350   

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