KEGG   PATHWAY: pvp04350
Entry
pvp04350                    Pathway                                
Name
TGF-beta signaling pathway - Pteropus vampyrus (large flying fox)
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
pvp04350  TGF-beta signaling pathway
pvp04350

Other DBs
GO: 0007179
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288464  [KO:K14736]
105288470  [KO:K14736]
105288602  GREM1; gremlin-1 isoform X1 [KO:K23318]
105288620  THBS1; thrombospondin-1 [KO:K16857]
105288777  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
105288810  FBN1; fibrillin-1 [KO:K06825]
105288917  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289544  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
105290266  RGMA; repulsive guidance molecule A [KO:K23096]
105290409  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
105290451  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
105290575  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105291301  NCOR1; nuclear receptor corepressor 1 isoform X3 [KO:K04650]
105291323  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
105291355  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
105291557  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
105291730  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
105292284  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
105292297  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105292451  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105292575  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
105292611  LEFTY2; left-right determination factor 2 [KO:K04668]
105292640  SMAD2; mothers against decapentaplegic homolog 2 isoform X3 [KO:K04500]
105292987  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
105293238  DCN; decorin [KO:K04660]
105293293  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
105293529  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
105293569  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
105293570  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
105293596  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
105293964  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
105295257  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105295374  NOG; noggin [KO:K04658]
105295433  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
105295648  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105295712  CUL1; cullin-1 isoform X1 [KO:K03347]
105296142  INHBB; inhibin beta B chain [KO:K22687]
105296163  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105296245  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
105296320  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
105296473  TGIF2; homeobox protein TGIF2 [KO:K19553]
105296511  RBL1; retinoblastoma-like protein 1 [KO:K04681]
105297107  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
105297622  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
105297710  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
105297740  HFE2; hemojuvelin [KO:K23100]
105298051  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
105298053  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105298112  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
105298319  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
105298440  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X4 [KO:K04685]
105298720  BMP2; bone morphogenetic protein 2 [KO:K21283]
105298780  BMP7; bone morphogenetic protein 7 [KO:K16621]
105298984  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X3 [KO:K04679]
105299206  TGFB3; transforming growth factor beta-3 [KO:K13377]
105299740  TFR2; transferrin receptor protein 2 [KO:K23910]
105299964  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105300066  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X13 [KO:K19559]
105300123  NODAL; nodal homolog [KO:K04666]
105300459  AMH; muellerian-inhibiting factor [KO:K04665]
105300596  GDF6; growth/differentiation factor 6 [KO:K20012]
105300693  FMOD; fibromodulin [KO:K08121]
105301182  LEMD3; inner nuclear membrane protein Man1 isoform X1 [KO:K19410]
105301262  IFNG; interferon gamma [KO:K04687]
105302075  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
105302100  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105302383  RHOA; transforming protein RhoA [KO:K04513]
105302645  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
105302654  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
105302655  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
105302747  E2F5; transcription factor E2F5 [KO:K04682]
105303098  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105303215  INHBA; inhibin beta A chain [KO:K04667]
105303329  NEO1; neogenin [KO:K06766]
105303611  SKI; ski oncogene [KO:K26503]
105303692  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
105304186  EMP3; epithelial membrane protein 3 [KO:K26257]
105304340  GDF5; growth/differentiation factor 5 [KO:K04664]
105304374  RGMB; RGM domain family member B [KO:K06847]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105305086  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
105305244  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
105305325  TNF; tumor necrosis factor [KO:K03156]
105305410  GREM2; gremlin-2 [KO:K23318]
105305501  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
105305629  SKIL; ski-like protein [KO:K18499]
105305708  E2F4; transcription factor E2F4 [KO:K04682]
105305798  FST; follistatin isoform X3 [KO:K04661]
105306550  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
105306596  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
105306631  HAMP; hepcidin [KO:K23106]
105306854  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
105307013  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
105307373  INHBC; inhibin beta C chain [KO:K22688]
105307374  INHBE; inhibin beta E chain [KO:K22689]
105307861  CHRD; chordin isoform X1 [KO:K04657]
105307945  TGFB1; transforming growth factor beta-1 [KO:K13375]
105308323  IGSF1; LOW QUALITY PROTEIN: immunoglobulin superfamily member 1 [KO:K26168]
105309232  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
105309722  NRROS; negative regulator of reactive oxygen species [KO:K26317]
105309732  TFRC; transferrin receptor protein 1 [KO:K06503]
105309746  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
105309787  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
105311216  [KO:K04685]
105311245  [KO:K16622]
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
pvp04010  MAPK signaling pathway
pvp04110  Cell cycle
pvp04120  Ubiquitin mediated proteolysis
pvp04210  Apoptosis
KO pathway
ko04350   

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