KEGG   PATHWAY: pgig04350
Entry
pgig04350                   Pathway                                
Name
TGF-beta signaling pathway - Pteropus giganteus (Indian 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
pgig04350  TGF-beta signaling pathway
pgig04350

Other DBs
GO: 0007179
Organism
Pteropus giganteus (Indian flying fox) [GN:pgig]
Gene
120592933  CHRD; chordin isoform X1 [KO:K04657]
120620781  NOG; noggin [KO:K04658]
120596159  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
120619058  GREM2; gremlin-2 isoform X1 [KO:K23318]
120587226  GREM1; gremlin-1 [KO:K23318]
120587198  THBS1; thrombospondin-1 [KO:K16857]
120607280  DCN; decorin [KO:K04660]
120617990  FMOD; fibromodulin isoform X1 [KO:K08121]
120619121  left-right determination factor 2-like [KO:K04668]
120619328  left-right determination factor 2 [KO:K04668]
120608169  FST; follistatin isoform X1 [KO:K04661]
120603409  BMP2; bone morphogenetic protein 2 [KO:K21283]
120604412  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
120607668  BMP6; bone morphogenetic protein 6 [KO:K16620]
120610346  INHBB; inhibin beta B chain [KO:K22687]
120582091  serotransferrin-like [KO:K14736]
120582092  inhibitor of carbonic anhydrase-like [KO:K14736]
120594850  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
120603859  BMP7; bone morphogenetic protein 7 [KO:K16621]
120614037  BMP8B; bone morphogenetic protein 8B [KO:K16622]
120593258  BMP8A; bone morphogenetic protein 8A [KO:K16622]
120603326  GDF5; growth/differentiation factor 5 [KO:K04664]
120605465  GDF6; growth/differentiation factor 6 [KO:K20012]
120622114  GDF7; growth/differentiation factor 7 [KO:K20013]
120583729  AMH; muellerian-inhibiting factor [KO:K04665]
120604831  IFNG; interferon gamma [KO:K04687]
120618944  TNF; tumor necrosis factor [KO:K03156]
120597829  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
120622675  FBN1; fibrillin-1 isoform X1 [KO:K06825]
120621791  LTBP1; LOW QUALITY PROTEIN: latent-transforming growth factor beta-binding protein 1 [KO:K19559]
120586591  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
120619172  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
120619522  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
120591502  INHBA; inhibin beta A chain isoform X1 [KO:K04667]
120604953  INHBC; inhibin beta C chain [KO:K22688]
120604952  INHBE; inhibin beta E chain [KO:K22689]
120609490  NODAL; nodal homolog [KO:K04666]
120609617  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
120588330  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
120597095  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
120587545  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
120597054  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
120585166  HJV; hemojuvelin isoform X1 [KO:K23100]
120597913  NEO1; neogenin isoform X1 [KO:K06766]
120606145  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
120591601  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
120593015  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
120587323  RGMA; repulsive guidance molecule A isoform X1 [KO:K23096]
120612578  RGMB; RGM domain family member B [KO:K06847]
120602178  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
120597204  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
120586804  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
120606981  EMP3; epithelial membrane protein 3 [KO:K26257]
120590376  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
120592916  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
120602113  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
120586741  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
120596906  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
120604297  IGSF1; LOW QUALITY PROTEIN: immunoglobulin superfamily member 1 [KO:K26168]
120584100  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
120613329  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
120581325  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
120610606  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
120585764  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120604483  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120585140  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
120604489  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
120585683  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
120616538  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
120600365  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
120620956  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
120612484  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
120602973  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120601485  CUL1; cullin-1 [KO:K03347]
120581290  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
120606851  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
120620121  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120582355  RHOA; transforming protein RhoA [KO:K04513]
120587763  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
120583980  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120621983  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120581292  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120589049  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120584753  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
120620825  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
120592501  hepcidin [KO:K23106]
120603513  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
120622067  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
120595988  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
120605574  ID4; DNA-binding protein inhibitor ID-4 isoform X1 [KO:K17695]
120603629  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
120585558  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
120615610  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
120602971  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
120620322  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
120602177  SP1; transcription factor Sp1 [KO:K04684]
120604378  SKIL; ski-like protein [KO:K18499]
120614118  SKI; ski oncogene [KO:K26503]
120597918  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
120581992  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
120608742  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
120589812  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
120588117  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
120603619  TGIF2; homeobox protein TGIF2 [KO:K19553]
120595433  MYC; myc proto-oncogene protein [KO:K04377]
120617116  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
120591131  PITX2; pituitary homeobox 2 [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
pgig04010  MAPK signaling pathway
pgig04110  Cell cycle
pgig04120  Ubiquitin mediated proteolysis
pgig04210  Apoptosis
KO pathway
ko04350   
LinkDB

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