KEGG   PATHWAY: opi04350
Entry
opi04350                    Pathway                                
Name
TGF-beta signaling pathway - Ochotona princeps (American pika)
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
opi04350  TGF-beta signaling pathway
opi04350

Other DBs
GO: 0007179
Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101523571  CHRD; chordin isoform X2 [KO:K04657]
101516765  NOG; noggin [KO:K04658]
101516527  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
101525719  GREM1; gremlin-1 isoform X1 [KO:K23318]
101528683  GREM2; gremlin-2 [KO:K23318]
101521365  THBS1; thrombospondin-1 [KO:K16857]
101536574  DCN; decorin isoform X2 [KO:K04660]
101520635  FMOD; fibromodulin [KO:K08121]
101529338  LEFTY1; left-right determination factor 1 isoform X1 [KO:K04668]
101520741  FST; follistatin isoform X1 [KO:K04661]
101523631  BMP2; bone morphogenetic protein 2 [KO:K21283]
101531889  BMP4; LOW QUALITY PROTEIN: bone morphogenetic protein 4 [KO:K04662]
101528443  BMP6; bone morphogenetic protein 6 [KO:K16620]
101536762  INHBB; inhibin beta B chain [KO:K22687]
101527397  serotransferrin isoform X2 [KO:K14736]
101527976  inhibitor of carbonic anhydrase-like [KO:K14736]
101516333  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
101522720  BMP7; bone morphogenetic protein 7 [KO:K16621]
101534077  bone morphogenetic protein 8A-like [KO:K16622]
101530851  GDF5; growth/differentiation factor 5 [KO:K04664]
101517462  GDF6; growth/differentiation factor 6 [KO:K20012]
101518538  GDF7; growth/differentiation factor 7 [KO:K20013]
101519639  AMH; muellerian-inhibiting factor [KO:K04665]
101517557  IFNG; interferon gamma [KO:K04687]
101525561  TNF; tumor necrosis factor isoform X2 [KO:K03156]
101534821  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
101522177  FBN1; fibrillin-1 [KO:K06825]
101527793  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
101533379  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
101529904  transforming growth factor beta-1 proprotein-like [KO:K13375]
101516556  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101525102  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101522112  INHBA; inhibin beta A chain [KO:K04667]
101523426  INHBC; inhibin beta C chain [KO:K22688]
101523675  INHBE; inhibin beta E chain [KO:K22689]
101516650  NODAL; nodal homolog [KO:K04666]
101534297  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101522569  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
101528675  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
101519164  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101536630  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
101535833  HJV; hemojuvelin isoform X1 [KO:K23100]
101516941  NEO1; neogenin isoform X1 [KO:K06766]
105942503  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
101525835  TFR2; transferrin receptor protein 2 [KO:K23910]
101519979  TFRC; transferrin receptor protein 1 [KO:K06503]
101521740  RGMA; repulsive guidance molecule A [KO:K23096]
101527805  RGMB; RGM domain family member B isoform X1 [KO:K06847]
101521699  anti-Muellerian hormone type-2 receptor-like [KO:K04672] [EC:2.7.11.30]
101521464  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
101533160  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
101534968  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
101531388  EMP3; epithelial membrane protein 3 [KO:K26257]
101528888  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
101521595  NRROS; transforming growth factor beta activator LRRC33 [KO:K26317]
101527295  ACVR1B; activin receptor type-1B [KO:K13567] [EC:2.7.11.30]
101535616  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
101528913  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
101517488  IGSF1; immunoglobulin superfamily member 1 isoform X1 [KO:K26168]
101519733  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
101521562  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101531816  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
101527268  SMAD9; mothers against decapentaplegic homolog 9 [KO:K16791]
101529841  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101532983  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101525575  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101520632  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
101529515  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
101525773  SMURF2; E3 ubiquitin-protein ligase SMURF2 isoform X1 [KO:K04678] [EC:2.3.2.26]
101529259  E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
101535668  E3 ubiquitin-protein ligase SMURF1-like [KO:K04678] [EC:2.3.2.26]
101517983  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
101520023  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
101519048  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
101529995  CUL1; cullin-1 [KO:K03347]
101526971  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101530701  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101525427  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101525255  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
101535305  transforming protein RhoA-like isoform X1 [KO:K04513]
101530829  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
101535531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
101518020  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101532400  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101527218  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101526118  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101528246  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101531691  hepcidin [KO:K23106]
101517899  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101518290  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101528492  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101536782  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
101516182  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101520002  E2F4; transcription factor E2F4 [KO:K04682]
101526243  E2F5; transcription factor E2F5 [KO:K04682]
101523250  TFDP1; transcription factor Dp-1 [KO:K04683]
101517073  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101518802  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101533630  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101519336  LOW QUALITY PROTEIN: ski-like protein [KO:K18499]
101533908  SKIL; ski-like protein [KO:K18499]
101535644  SKI; ski oncogene [KO:K26503]
101532410  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
101518320  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101529108  LOW QUALITY PROTEIN: histone deacetylase 2-like [KO:K06067] [EC:3.5.1.98]
101518852  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101517215  NCOR1; LOW QUALITY PROTEIN: nuclear receptor corepressor 1 [KO:K04650]
101533872  TGIF1; homeobox protein TGIF1 isoform X1 [KO:K19383]
105941503  TGIF2; homeobox protein TGIF2 isoform X1 [KO:K19553]
101522285  MYC; myc proto-oncogene protein [KO:K04377]
101527626  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101527165  PITX2; pituitary homeobox 2 isoform X1 [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
opi04010  MAPK signaling pathway
opi04110  Cell cycle
opi04120  Ubiquitin mediated proteolysis
opi04210  Apoptosis
KO pathway
ko04350   
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