KEGG   PATHWAY: fca04350
Entry
fca04350                    Pathway                                
Name
TGF-beta signaling pathway - Felis catus (domestic cat)
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
fca04350  TGF-beta signaling pathway
fca04350

Other DBs
GO: 0007179
Organism
Felis catus (domestic cat) [GN:fca]
Gene
100301987  BMP2; bone morphogenetic protein 2 isoform X2 [KO:K21283]
100379628  MYC; myc proto-oncogene protein [KO:K04377]
101080263  AMH; muellerian-inhibiting factor [KO:K04665]
101081075  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101081219  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
101081533  GDF5; growth/differentiation factor 5 [KO:K04664]
101081602  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101082086  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
101082489  BMPR1B; bone morphogenetic protein receptor type-1B isoform X3 [KO:K13578] [EC:2.7.11.30]
101083726  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101084045  [KO:K03094]
101084176  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
101084332  [KO:K23106]
101084534  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X7 [KO:K19559]
101084643  INHBB; inhibin beta B chain [KO:K22687]
101084747  TGIF1; homeobox protein TGIF1 [KO:K19383]
101084882  FBN1; fibrillin-1 [KO:K06825]
101084960  HFE; hereditary hemochromatosis protein isoform X3 [KO:K26535]
101085148  [KO:K14736]
101085162  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
101085713  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101085902  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
101085942  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
101086029  [KO:K04668]
101086087  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
101086915  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
101087014  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101087051  CUL1; cullin-1 isoform X3 [KO:K03347]
101087179  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101087448  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
101087599  INHCA; inhibitor of carbonic anhydrase [KO:K14736]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087758  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101088165  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
101088277  SMAD7; mothers against decapentaplegic homolog 7 isoform X2 [KO:K19631]
101088344  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
101088346  SKI; ski oncogene isoform X1 [KO:K26503]
101088446  EMP3; epithelial membrane protein 3 [KO:K26257]
101089375  BMP8A; bone morphogenetic protein 8A isoform X1 [KO:K16622]
101089491  RGMB; repulsive guidance molecule B isoform X2 [KO:K06847]
101089548  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101089642  LRRC32; transforming growth factor beta activator LRRC32 isoform X1 [KO:K26316]
101089985  FST; follistatin isoform X1 [KO:K04661]
101090256  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101090533  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
101090620  NEO1; neogenin isoform X1 [KO:K06766]
101091037  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
101091298  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101091725  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
101091798  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
101091812  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X3 [KO:K04688] [EC:2.7.11.1]
101091838  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
101092197  INHBC; inhibin beta C chain [KO:K22688]
101092198  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
101092447  INHBE; inhibin beta E chain [KO:K22689]
101092552  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
101092561  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X2 [KO:K04688] [EC:2.7.11.1]
101092657  TFR2; transferrin receptor protein 2 isoform X2 [KO:K23910]
101092689  THBS1; thrombospondin-1 [KO:K16857]
101093414  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
101093650  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101094057  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
101094168  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
101094183  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X4 [KO:K23377]
101094471  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101094667  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101094693  CHRD; chordin isoform X1 [KO:K04657]
101095019  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
101095164  RBL1; retinoblastoma-like protein 1 isoform X2 [KO:K04681]
101095216  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X5 [KO:K04678] [EC:2.3.2.26]
101095293  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
101096338  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101096531  GREM2; gremlin-2 isoform X1 [KO:K23318]
101096571  RGMA; repulsive guidance molecule A [KO:K23096]
101096594  SKIL; ski-like protein [KO:K18499]
101096673  NODAL; nodal homolog [KO:K04666]
101096735  GREM1; gremlin-1 [KO:K23318]
101096875  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
101097058  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101097137  TGIF2; homeobox protein TGIF2 [KO:K19553]
101097318  BMP5; bone morphogenetic protein 5 [KO:K04663]
101097654  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
101097750  ACVR2A; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
101098313  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101098469  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101098635  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
101098870  BMP6; bone morphogenetic protein 6 [KO:K16620]
101098911  E2F4; transcription factor E2F4 [KO:K04682]
101099017  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101099043  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
101099228  HDAC1; histone deacetylase 1 isoform X3 [KO:K06067] [EC:3.5.1.98]
101099271  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
101099991  HJV; hemojuvelin isoform X3 [KO:K23100]
101100227  SP1; transcription factor Sp1 [KO:K04684]
101100311  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
101101027  FMOD; fibromodulin [KO:K08121]
101101236  DCN; decorin [KO:K04660]
101101387  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102901566  [KO:K16622]
105260113  NOG; noggin [KO:K04658]
105261327  [KO:K04668]
111558542  GDF6; growth/differentiation factor 6 [KO:K20012]
111559870  GDF7; growth/differentiation factor 7 [KO:K20013]
111561294  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493853  INHBA; inhibin beta A chain precursor [KO:K04667]
493880  TFRC; transferrin receptor protein 1 [KO:K06503]
493965  IFNG; interferon gamma precursor [KO:K04687]
768263  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
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
fca04010  MAPK signaling pathway
fca04110  Cell cycle
fca04120  Ubiquitin mediated proteolysis
fca04210  Apoptosis
KO pathway
ko04350   

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