KEGG   PATHWAY: mna04350
Entry
mna04350                    Pathway                                
Name
TGF-beta signaling pathway - Miniopterus natalensis (Natal long-fingered bat)
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
mna04350  TGF-beta signaling pathway
mna04350

Other DBs
GO: 0007179
Organism
Miniopterus natalensis (Natal long-fingered bat) [GN:mna]
Gene
107523767  CUL1; cullin-1 isoform X1 [KO:K03347]
107524250  GREM2; gremlin-2 [KO:K23318]
107524303  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
107524488  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
107524503  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
107525009  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
107525161  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
107525371  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
107525394  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107525395  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
107525560  RGMA; repulsive guidance molecule A [KO:K23096]
107525808  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
107525879  BMP4; bone morphogenetic protein 4 [KO:K04662]
107525935  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
107526075  NODAL; nodal homolog [KO:K04666]
107526381  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
107526468  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
107526675  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
107526705  TMEM53; transmembrane protein 53 [KO:K28359]
107527069  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
107527155  FST; follistatin [KO:K04661]
107527227  IFNG; interferon gamma [KO:K04687]
107527264  TFRC; transferrin receptor protein 1 [KO:K06503]
107527407  NRROS; negative regulator of reactive oxygen species [KO:K26317]
107527734  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
107527879  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
107528186  AMHR2; LOW QUALITY PROTEIN: anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
107528249  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
107528284  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
107528307  SP1; transcription factor Sp1 [KO:K04684]
107528447  NEO1; neogenin isoform X1 [KO:K06766]
107529064  HFE2; hemojuvelin [KO:K23100]
107529113  BMP6; bone morphogenetic protein 6 [KO:K16620]
107529258  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
107529450  RHOA; transforming protein RhoA [KO:K04513]
107529539  SKIL; ski-like protein [KO:K18499]
107529673  BMP7; bone morphogenetic protein 7 [KO:K16621]
107530082  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107530913  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
107531277  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
107531280  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
107531299  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
107531463  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
107531859  EMP3; epithelial membrane protein 3 [KO:K26257]
107531931  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
107532516  SMAD1; mothers against decapentaplegic homolog 1 isoform X1 [KO:K04676]
107532534  PITX2; pituitary homeobox 2 [KO:K04686]
107533732  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
107533843  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
107533955  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
107534103  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107534176  TGFB1; transforming growth factor beta-1 [KO:K13375]
107534547  AMH; muellerian-inhibiting factor [KO:K04665]
107534633  INHBB; inhibin beta B chain [KO:K22687]
107535036  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
107535189  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
107535411  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
107535590  FBN1; fibrillin-1 [KO:K06825]
107535781  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
107535888  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
107535907  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
107536120  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
107536373  BMP2; bone morphogenetic protein 2 isoform X1 [KO:K21283]
107536955  TFDP1; transcription factor Dp-1 [KO:K04683]
107537217  GDF5; growth/differentiation factor 5 [KO:K04664]
107537262  INHBA; inhibin beta A chain [KO:K04667]
107537414  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
107537473  E2F4; transcription factor E2F4 [KO:K04682]
107538350  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
107538354  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
107538481  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
107538543  FMOD; fibromodulin [KO:K08121]
107538917  DCN; decorin [KO:K04660]
107538974  TNF; tumor necrosis factor [KO:K03156]
107539494  MYC; myc proto-oncogene protein [KO:K04377]
107539619  RGMB; RGM domain family member B [KO:K06847]
107540143  SKI; ski oncogene [KO:K26503]
107540441  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107540705  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
107540819  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
107540969  TFR2; transferrin receptor protein 2 [KO:K23910]
107541193  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107541712  BMP8A; LOW QUALITY PROTEIN: bone morphogenetic protein 8A [KO:K16622]
107541772  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
107542095  RBL1; retinoblastoma-like protein 1 [KO:K04681]
107542136  TGIF2; homeobox protein TGIF2 [KO:K19553]
107543012  THBS1; thrombospondin-1 isoform X1 [KO:K16857]
107543020  GREM1; gremlin-1 [KO:K23318]
107543118  [KO:K04657]
107543458  HAMP; hepcidin [KO:K23106]
107543594  [KO:K04668]
107543602  [KO:K04668]
107543622  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
107544970  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
107546066  [KO:K14736]
107546068  [KO:K14736]
107546161  INHBC; inhibin beta C chain [KO:K22688]
107546162  INHBE; inhibin beta E chain [KO:K22689]
107546622  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
107546624  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
107546640  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
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
mna04010  MAPK signaling pathway
mna04110  Cell cycle
mna04120  Ubiquitin mediated proteolysis
mna04210  Apoptosis
KO pathway
ko04350   

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