KEGG   PATHWAY: uar04350
Entry
uar04350                    Pathway                                
Name
TGF-beta signaling pathway - Ursus americanus (American black 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
uar04350  TGF-beta signaling pathway
uar04350

Other DBs
GO: 0007179
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123776110  [KO:K16622]
123776114  BMP8B; bone morphogenetic protein 8B isoform X1 [KO:K16622]
123776366  EMP3; epithelial membrane protein 3 [KO:K26257]
123776752  TFDP1; transcription factor Dp-1 [KO:K04683]
123776971  NOG; noggin [KO:K04658]
123777184  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
123777311  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
123777686  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
123777991  [KO:K03456]
123778404  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
123778562  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
123778691  HJV; hemojuvelin isoform X1 [KO:K23100]
123778975  CHRD; chordin isoform X1 [KO:K04657]
123779776  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
123780073  RHOA; transforming protein RhoA [KO:K04513]
123780194  [KO:K26168]
123780362  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123780699  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
123780775  DCN; decorin [KO:K04660]
123780918  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
123781069  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
123781261  [KO:K04685]
123781814  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
123781846  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
123781850  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
123782062  TGIF1; homeobox protein TGIF1 [KO:K19383]
123782085  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
123782213  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
123782225  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
123782324  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
123782386  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
123782985  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
123783080  NODAL; nodal homolog [KO:K04666]
123783593  [KO:K04498] [EC:2.3.1.48]
123784602  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123785715  FMOD; fibromodulin [KO:K08121]
123786381  SKIL; ski-like protein [KO:K18499]
123787164  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
123787219  INHBC; inhibin beta C chain [KO:K22688]
123787294  IFNG; interferon gamma [KO:K04687]
123787305  INHBE; inhibin beta E chain [KO:K22689]
123787367  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
123787372  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
123787394  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
123788389  [KO:K14736]
123788391  [KO:K14736]
123788609  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
123788818  CUL1; cullin-1 [KO:K03347]
123789441  INHBA; inhibin beta A chain [KO:K04667]
123790326  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
123790348  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123790350  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
123790664  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
123790702  NEO1; neogenin isoform X1 [KO:K06766]
123790717  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
123791076  TNF; tumor necrosis factor [KO:K03156]
123791167  GREM2; gremlin-2 [KO:K23318]
123791528  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
123791713  [KO:K23106]
123791907  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
123792556  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
123792602  LEFTY1; left-right determination factor 1 isoform X1 [KO:K04668]
123792830  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
123792970  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
123793242  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
123793353  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
123793693  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
123793785  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
123793952  AMH; muellerian-inhibiting factor [KO:K04665]
123794205  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
123794697  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
123794698  SP1; transcription factor Sp1 [KO:K04684]
123794730  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
123795639  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123795781  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
123796124  SKI; ski oncogene isoform X1 [KO:K26503]
123796601  INHBB; inhibin beta B chain [KO:K22687]
123796950  TGIF2; homeobox protein TGIF2 [KO:K19553]
123796962  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
123797675  GDF6; growth/differentiation factor 6 [KO:K20012]
123797922  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
123797944  GDF5; growth/differentiation factor 5 [KO:K04664]
123798214  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
123798962  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123799286  RGMB; LOW QUALITY PROTEIN: repulsive guidance molecule B [KO:K06847]
123799365  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
123799694  BMP2; bone morphogenetic protein 2 [KO:K21283]
123799846  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
123800112  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123800425  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
123800688  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
123800767  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
123800821  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
123801578  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
123801596  BMP6; LOW QUALITY PROTEIN: bone morphogenetic protein 6 [KO:K16620]
123801871  FBN1; fibrillin-1 [KO:K06825]
123801908  MYC; myc proto-oncogene protein [KO:K04377]
123802115  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
123802150  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
123802256  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
123802413  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
123802558  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
123802615  GDF7; growth/differentiation factor 7 [KO:K20013]
123803252  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
123803510  E2F4; transcription factor E2F4 [KO:K04682]
123803698  FST; follistatin isoform X1 [KO:K04661]
123803958  GREM1; gremlin-1 [KO:K23318]
123804137  THBS1; thrombospondin-1 [KO:K16857]
123804227  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
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
uar04010  MAPK signaling pathway
uar04110  Cell cycle
uar04120  Ubiquitin mediated proteolysis
uar04210  Apoptosis
KO pathway
ko04350   

DBGET integrated database retrieval system