KEGG   PATHWAY: ssc04350
Entry
ssc04350                    Pathway                                
Name
TGF-beta signaling pathway - Sus scrofa (pig)
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
ssc04350  TGF-beta signaling pathway
ssc04350

Other DBs
GO: 0007179
Organism
Sus scrofa (pig) [GN:ssc]
Gene
100038019  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100113425  BMP4; bone morphogenetic protein 4 precursor [KO:K04662]
100127158  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100127483  BMPR2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:2.7.11.30]
100144508  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
100151964  BMP5; bone morphogenetic protein 5 [KO:K04663]
100152069  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
100152307  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
100152462  ACVR1B; activin receptor type-1B precursor [KO:K13567] [EC:2.7.11.30]
100153296  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100153567  SKIL; ski-like protein isoform X1 [KO:K18499]
100153584  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100154297  AMHR2; anti-Muellerian hormone type-2 receptor precursor [KO:K04672] [EC:2.7.11.30]
100155304  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
100155536  BMP6; bone morphogenetic protein 6 precursor [KO:K16620]
100155778  HFE2; hemojuvelin isoform X2 [KO:K23100]
100156170  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100156226  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100156280  GREM1; gremlin-1 isoform X1 [KO:K23318]
100156429  RGMA; repulsive guidance molecule A isoform X2 [KO:K23096]
100156756  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
100157103  BMP2; bone morphogenetic protein 2 precursor [KO:K21283]
100157227  IGSF1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
100157957  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
100169652  BMPR1A; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:2.7.11.30]
100337677  LEFTY2; left-right determination factor 2 precursor [KO:K04668]
100510914  NEO1; neogenin isoform X1 [KO:K06766]
100511508  LEMD3; LEM domain containing 3 [KO:K19410]
100511806  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
100512153  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100515395  PITX2; pituitary homeobox 2 [KO:K04686]
100515668  BMP8A; LOW QUALITY PROTEIN: bone morphogenetic protein 8A [KO:K16622]
100517164  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
100517580  TFR2; transferrin receptor protein 2 isoform X2 [KO:K23910]
100518554  INHBE; LOW QUALITY PROTEIN: inhibin beta E chain [KO:K22689]
100520183  [KO:K03094]
100520988  GDF5; growth/differentiation factor 5 precursor [KO:K04664]
100521305  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
100521329  GREM2; gremlin-2 [KO:K23318]
100522452  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
100522677  E2F4; transcription factor E2F4 [KO:K04682]
100522839  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100524037  CUL1; cullin-1 [KO:K03347]
100524417  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X2 [KO:K23377]
100524517  [KO:K04668]
100526237  FMOD; fibromodulin [KO:K08121]
100620084  INHBC; inhibin beta C chain [KO:K22688]
100620215  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100620350  CHRD; chordin isoform X14 [KO:K04657]
100620374  BMP8B; LOW QUALITY PROTEIN: bone morphogenetic protein 8B [KO:K16622]
100620479  NRROS; negative regulator of reactive oxygen species [KO:K26317]
100621036  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
100621221  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
100621443  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
100622482  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100623582  NBL1; neuroblastoma suppressor of tumorigenicity 1 isoform X1 [KO:K19558]
100624262  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
100624534  GDF7; growth/differentiation factor 7 isoform X1 [KO:K20013]
100625126  EMP3; epithelial membrane protein 3 [KO:K26257]
100625732  TGIF1; homeobox protein TGIF1 isoform c [KO:K19383]
100626978  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100627243  LTBP1; LOW QUALITY PROTEIN: latent-transforming growth factor beta-binding protein 1 [KO:K19559]
100627676  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
100628075  NCOR1; LOW QUALITY PROTEIN: nuclear receptor corepressor 1 [KO:K04650]
100737299  RGMB; LOW QUALITY PROTEIN: RGM domain family member B [KO:K06847]
100739435  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
110256843  NODAL; nodal homolog [KO:K04666]
110257437  TGIF2; homeobox protein TGIF2 [KO:K19553]
110259483  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
110260254  GDF6; growth/differentiation factor 6 [KO:K20012]
110260638  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
110261080  SKI; ski oncogene [KO:K26503]
110261476  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
396575  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
396665  TGFBR1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
396691  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
396845  ICA; inhibitor of carbonic anhydrase precursor [KO:K14736]
396849  RHOA; transforming protein RhoA [KO:K04513]
396957  DCN; decorin precursor [KO:K04660]
396991  IFNG; interferon gamma precursor [KO:K04687]
396996  TF; serotransferrin precursor [KO:K14736]
397016  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
397062  TFRC; transferrin receptor protein 1 [KO:K06503]
397078  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
397084  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
397086  TNF; tumor necrosis factor [KO:K03156]
397088  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
397093  INHBA; inhibin beta A chain precursor [KO:K04667]
397136  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
397142  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
397207  HAMP; hepcidin precursor [KO:K23106]
397227  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
397260  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
397282  ACVR2A; activin receptor type-2A precursor [KO:K04670] [EC:2.7.11.30]
397400  TGFB3; transforming growth factor beta-3 precursor [KO:K13377]
397447  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
397470  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
397490  INHBB; inhibin beta B chain precursor [KO:K22687]
397578  AMH; muellerian-inhibiting factor precursor [KO:K04665]
397656  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
414836  FBN1; fibrillin-1 precursor [KO:K06825]
445002  FST; follistatin precursor [KO:K04661]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
448810  MYC; myc proto-oncogene protein [KO:K04377]
448845  ACVR2B; activin receptor type-2B precursor [KO:K13596] [EC:2.7.11.30]
449001  BAMBI; BMP and activin membrane-bound inhibitor homolog precursor [KO:K10162]
492313  THBS1; thrombospondin-1 precursor [KO:K16857]
492315  BMP7; bone morphogenetic protein 7 precursor [KO:K16621]
574073  NOG; noggin precursor [KO:K04658]
654298  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
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
ssc04010  MAPK signaling pathway
ssc04110  Cell cycle
ssc04120  Ubiquitin mediated proteolysis
ssc04210  Apoptosis
KO pathway
ko04350   

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