KEGG   PATHWAY: umr04350
Entry
umr04350                    Pathway                                
Name
TGF-beta signaling pathway - Ursus maritimus (polar bear)
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
umr04350  TGF-beta signaling pathway
umr04350

Other DBs
GO: 0007179
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656491  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
103656558  INHBC; inhibin beta C chain [KO:K22688]
103656569  INHBE; inhibin beta E chain [KO:K22689]
103656858  IFNG; interferon gamma [KO:K04687]
103656870  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
103656960  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
103657229  EMP3; epithelial membrane protein 3 [KO:K26257]
103657330  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X5 [KO:K03456]
103657613  TFDP1; transcription factor Dp-1 [KO:K04683]
103657735  FMOD; fibromodulin [KO:K08121]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103657993  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
103658194  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103658515  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
103658626  INHBB; inhibin beta B chain [KO:K22687]
103659105  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103659481  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
103659482  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
103659757  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
103660048  RGMA; repulsive guidance molecule A [KO:K23096]
103660083  DCN; decorin [KO:K04660]
103661461  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
103661630  GDF6; growth/differentiation factor 6 [KO:K20012]
103661697  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103661749  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
103662531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103662622  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
103662842  ROCK1; rho-associated protein kinase 1 isoform X3 [KO:K04514] [EC:2.7.11.39]
103663799  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
103663817  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
103663939  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103663983  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
103664035  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
103664305  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
103664375  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
103664631  FST; follistatin isoform X1 [KO:K04661]
103665146  BMP6; bone morphogenetic protein 6 [KO:K16620]
103665189  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
103665650  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
103666443  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103666562  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
103666706  BMP8A; bone morphogenetic protein 8A [KO:K16622]
103666811  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
103667329  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
103667475  NOG; noggin [KO:K04658]
103667704  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
103667794  NODAL; nodal homolog [KO:K04666]
103667882  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
103668810  [KO:K04498] [EC:2.3.1.48]
103668912  [KO:K23318]
103668956  CUL1; cullin-1 [KO:K03347]
103669043  [KO:K04668]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103669778  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103669788  TGIF2; homeobox protein TGIF2 [KO:K19553]
103669911  GDF5; growth/differentiation factor 5 [KO:K04664]
103669981  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
103670116  TFR2; transferrin receptor protein 2 [KO:K23910]
103670715  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
103670791  TMEM53; transmembrane protein 53 [KO:K28359]
103670922  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103670970  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
103671591  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
103672235  RGMB; RGM domain family member B [KO:K06847]
103672937  IGSF1; immunoglobulin superfamily member 1 isoform X2 [KO:K26168]
103672975  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
103673473  THBS1; thrombospondin-1 [KO:K16857]
103673497  GREM1; gremlin-1 isoform X1 [KO:K23318]
103673668  E2F4; transcription factor E2F4 [KO:K04682]
103674159  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103674160  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
103674423  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
103674477  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
103674587  INHBA; inhibin beta A chain [KO:K04667]
103674825  RHOA; transforming protein RhoA [KO:K04513]
103675499  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
103675530  SP1; transcription factor Sp1 [KO:K04684]
103675532  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
103676155  SKIL; ski-like protein isoform X1 [KO:K18499]
103676180  CHRD; LOW QUALITY PROTEIN: chordin [KO:K04657]
103676717  FBN1; fibrillin-1 [KO:K06825]
103676974  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103677394  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
103677908  BMPR1B; bone morphogenetic protein receptor type-1B isoform X2 [KO:K13578] [EC:2.7.11.30]
103678129  LRRC32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
103678363  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
103678427  HJV; hemojuvelin [KO:K23100]
103678448  SKI; ski oncogene [KO:K26503]
103678627  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
103678941  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
103678957  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
103678978  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
103678998  [KO:K14736]
103679015  [KO:K14736]
103679059  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
103679134  NEO1; neogenin [KO:K06766]
103679143  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
103679154  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103679516  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
103679831  [KO:K04685]
103680677  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
103681466  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
103682015  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
103682322  TNF; tumor necrosis factor [KO:K03156]
103682405  [KO:K16622]
103682498  [KO:K23106]
121100753  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
121100971  GDF7; growth/differentiation factor 7 [KO:K20013]
121102581  AMH; LOW QUALITY PROTEIN: muellerian-inhibiting factor [KO:K04665]
121103983  GREM2; gremlin-2 [KO:K23318]
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
umr04010  MAPK signaling pathway
umr04110  Cell cycle
umr04120  Ubiquitin mediated proteolysis
umr04210  Apoptosis
KO pathway
ko04350   

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