KEGG   PATHWAY: pleu04350
Entry
pleu04350                   Pathway                                
Name
TGF-beta signaling pathway - Peromyscus leucopus (white-footed mouse)
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
pleu04350  TGF-beta signaling pathway
pleu04350

Other DBs
GO: 0007179
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114683318  Chrd; chordin isoform X1 [KO:K04657]
114699244  Nog; noggin [KO:K04658]
114697179  neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
114690671  Grem2; gremlin-2 [KO:K23318]
114697500  Grem1; gremlin-1 [KO:K23318]
114705915  Thbs1; LOW QUALITY PROTEIN: thrombospondin-1 [KO:K16857]
114701202  Dcn; decorin [KO:K04660]
114698100  Fmod; fibromodulin [KO:K08121]
114690714  left-right determination factor 1 [KO:K04668]
114690715  left-right determination factor 2 isoform X2 [KO:K04668]
114686405  LOW QUALITY PROTEIN: left-right determination factor 1-like [KO:K04668]
114703713  Fst; follistatin isoform X1 [KO:K04661]
114699539  Bmp2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
114696047  Bmp4; bone morphogenetic protein 4 [KO:K04662]
114710567  Bmp6; bone morphogenetic protein 6 [KO:K16620]
114700235  Inhbb; LOW QUALITY PROTEIN: inhibin beta B chain [KO:K22687]
114693526  LOW QUALITY PROTEIN: inhibitor of carbonic anhydrase [KO:K14736]
114693527  LOW QUALITY PROTEIN: serotransferrin-like [KO:K14736]
114690275  Bmp5; bone morphogenetic protein 5 [KO:K04663]
114709820  Bmp7; bone morphogenetic protein 7 [KO:K16621]
114681161  bone morphogenetic protein 8A-like [KO:K16622]
114681165  bone morphogenetic protein 8A [KO:K16622]
114706531  Gdf5; growth/differentiation factor 5 [KO:K04664]
114699428  growth/differentiation factor 6-like [KO:K20012]
114707598  LOW QUALITY PROTEIN: growth/differentiation factor 6-like [KO:K20012]
114692035  growth/differentiation factor 7 [KO:K20013]
114686522  Amh; muellerian-inhibiting factor [KO:K04665]
114693330  Ifng; interferon gamma [KO:K04687]
114705817  Tnf; tumor necrosis factor [KO:K03156]
114687321  Thsd4; thrombospondin type-1 domain-containing protein 4 isoform X2 [KO:K23377]
114683899  Fbn1; fibrillin-1 isoform X1 [KO:K06825]
114695932  Ltbp1; LOW QUALITY PROTEIN: latent-transforming growth factor beta-binding protein 1 [KO:K19559]
114685302  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
114698210  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
114697904  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
114685392  Inhba; inhibin beta A chain [KO:K04667]
114704780  Inhbc; inhibin beta C chain [KO:K22688]
114704830  Inhbe; inhibin beta E chain [KO:K22689]
114704728  Nodal; nodal homolog [KO:K04666]
114699332  Bmpr1a; bone morphogenetic protein receptor type-1A isoform X1 [KO:K04673] [EC:2.7.11.30]
114681722  Bmpr1b; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
114695638  Acvr1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
114685750  Bmpr2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
114700439  Acvr2a; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
114680923  Hjv; hemojuvelin [KO:K23100]
114708914  Neo1; neogenin isoform X1 [KO:K06766]
114700268  Hfe; hereditary hemochromatosis protein [KO:K26535]
114686785  Tfr2; LOW QUALITY PROTEIN: transferrin receptor protein 2 [KO:K23910]
114685390  Tfrc; LOW QUALITY PROTEIN: transferrin receptor protein 1 [KO:K06503]
114709442  Rgma; repulsive guidance molecule A [KO:K23096]
114691321  Rgmb; RGM domain family member B [KO:K06847]
114696624  Amhr2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
114691745  LOW QUALITY PROTEIN: TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
114690920  TGF-beta receptor type-1-like [KO:K04674] [EC:2.7.11.30]
114702344  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
114704977  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
114684724  Emp3; epithelial membrane protein 3 [KO:K26257]
114698687  Lrrc32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
114710037  Nrros; transforming growth factor beta activator LRRC33 isoform X2 [KO:K26317]
114696657  Acvr1b; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
114682495  Acvr2b; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
114695884  Acvr1c; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
114710164  immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
114709215  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
114688821  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
114695873  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
114694883  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
114691539  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
114690183  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
114691531  Smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
114694878  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
114690425  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
114707571  Smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
114682164  Zfyve16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
114706315  Zfyve9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
114707186  E3 ubiquitin-protein ligase RBX1-like [KO:K03868] [EC:2.3.2.32]
114694298  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
114698005  Cul1; cullin-1 [KO:K03347]
114683050  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
114699340  S-phase kinase-associated protein 1-like [KO:K03094]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114710523  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
114705216  Rhoa; transforming protein RhoA [KO:K04513]
114700910  transforming protein RhoA-like [KO:K04513]
114698172  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
114690258  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X2 [KO:K03456]
114686858  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
114683042  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
114698498  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
114685999  Rps6kb2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
114699281  Rps6kb1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
114698939  hepcidin isoform X1 [KO:K23106]
114705578  Id1; DNA-binding protein inhibitor ID-1 isoform X1 [KO:K04680]
114709772  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
114697225  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
114692059  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
114681841  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
114681033  E2f4; transcription factor E2F4 [KO:K04682]
114704095  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
114701239  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
114694299  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
114710614  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
114696625  Sp1; transcription factor Sp1 isoform X1 [KO:K04684]
114695316  Skil; ski-like protein isoform X1 [KO:K18499]
114708253  Ski; ski oncogene isoform X1 [KO:K26503]
114690326  Sin3a; paired amphipathic helix protein Sin3a [KO:K11644]
114683075  histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
114705645  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
114696875  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
114682964  Ncor1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
114681957  homeobox protein TGIF1-like [KO:K19383]
114696412  Tgif1; homeobox protein TGIF1 isoform X1 [KO:K19383]
114681839  Tgif2; homeobox protein TGIF2 [KO:K19553]
114701991  Myc; myc proto-oncogene protein [KO:K04377]
114698354  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
114682646  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
pleu04010  MAPK signaling pathway
pleu04110  Cell cycle
pleu04120  Ubiquitin mediated proteolysis
pleu04210  Apoptosis
KO pathway
ko04350   
LinkDB

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