KEGG   PATHWAY: sara04350
Entry
sara04350                   Pathway                                
Name
TGF-beta signaling pathway - Sorex araneus (European shrew)
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
sara04350  TGF-beta signaling pathway
sara04350

Other DBs
GO: 0007179
Organism
Sorex araneus (European shrew) [GN:sara]
Gene
101536998  E2F5; transcription factor E2F5 [KO:K04682]
101537103  TGIF1; homeobox protein TGIF1 isoform X2 [KO:K19383]
101537163  TMEM53; transmembrane protein 53 [KO:K28359]
101537309  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
101537391  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101537676  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
101537770  TFRC; transferrin receptor protein 1 [KO:K06503]
101538240  [KO:K06067] [EC:3.5.1.98]
101538267  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
101538340  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101538360  FMOD; fibromodulin [KO:K08121]
101538844  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101538864  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
101539626  BMPR1B; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:2.7.11.30]
101539682  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
101540080  BMP4; bone morphogenetic protein 4 [KO:K04662]
101540641  NOG; noggin [KO:K04658]
101540691  BMP7; bone morphogenetic protein 7 [KO:K16621]
101540972  IFNG; interferon gamma [KO:K04687]
101540987  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.39]
101541370  NODAL; nodal homolog [KO:K04666]
101541387  MYC; myc proto-oncogene protein [KO:K04377]
101541400  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
101541437  INHBB; inhibin beta B chain [KO:K22687]
101541587  [KO:K04371] [EC:2.7.11.24]
101541603  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101541743  GDF6; growth/differentiation factor 6 [KO:K20012]
101541867  ACVR1C; activin receptor type-1C isoform X1 [KO:K13568] [EC:2.7.11.30]
101542180  HFE2; hemojuvelin [KO:K23100]
101542238  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101542504  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101542694  BMP5; bone morphogenetic protein 5 [KO:K04663]
101542840  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
101543049  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
101543447  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101543797  DCN; decorin isoform X1 [KO:K04660]
101543926  ACVR2B; activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
101544191  [KO:K04513]
101544311  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
101544435  GDF5; growth/differentiation factor 5 [KO:K04664]
101544526  THSD4; thrombospondin type-1 domain-containing protein 4 [KO:K23377]
101544545  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
101544572  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
101544827  BMP6; bone morphogenetic protein 6 [KO:K16620]
101544943  [KO:K04668]
101545056  GREM1; gremlin-1 isoform X1 [KO:K23318]
101545091  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
101545201  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
101545278  TFDP1; transcription factor Dp-1 [KO:K04683]
101545316  CUL1; cullin-1 [KO:K03347]
101545473  [KO:K04668]
101545645  CHRD; chordin [KO:K04657]
101545683  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
101545848  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101546290  TGFB3; transforming growth factor beta-3 [KO:K13377]
101546769  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
101546905  NEO1; neogenin [KO:K06766]
101547889  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101547945  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
101547987  RGMA; repulsive guidance molecule A [KO:K23096]
101548404  BMP2; bone morphogenetic protein 2 [KO:K21283]
101548814  [KO:K16620]
101549042  SMAD7; mothers against decapentaplegic homolog 7 isoform X1 [KO:K19631]
101549205  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
101549293  PITX2; pituitary homeobox 2 [KO:K04686]
101549465  THBS1; thrombospondin-1 [KO:K16857]
101550076  FBN1; fibrillin-1 [KO:K06825]
101550205  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
101550225  BAMBI; BMP and activin membrane-bound inhibitor homolog [KO:K10162]
101550456  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
101550656  NRROS; negative regulator of reactive oxygen species [KO:K26317]
101550757  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101550764  GDF7; growth/differentiation factor 7 [KO:K20013]
101550783  [KO:K16622]
101551346  TGFB1; transforming growth factor beta-1 [KO:K13375]
101551747  FST; follistatin isoform X1 [KO:K04661]
101551851  [KO:K16622]
101552483  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101552612  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
101552937  GREM2; gremlin-2 [KO:K23318]
101553015  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
101553110  RGMB; RGM domain family member B [KO:K06847]
101553463  SKIL; ski-like protein isoform X1 [KO:K18499]
101553495  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
101553684  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101554111  [KO:K03868] [EC:2.3.2.32]
101554159  SMURF1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:2.3.2.26]
101555340  INHBC; inhibin beta C chain [KO:K22688]
101555439  INHBE; inhibin beta E chain [KO:K22689]
101555779  [KO:K14736]
101555781  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101555829  ACVR2A; activin receptor type-2A [KO:K04670] [EC:2.7.11.30]
101556047  [KO:K14736]
101556154  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
101556301  E2F4; transcription factor E2F4 [KO:K04682]
101556969  INHBA; inhibin beta A chain [KO:K04667]
101557020  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101557286  TFR2; transferrin receptor protein 2 [KO:K23910]
101557390  HAMP; hepcidin [KO:K23106]
101557527  [KO:K04513]
101557763  HFE; hereditary hemochromatosis protein [KO:K26535]
101557964  SKI; ski oncogene [KO:K26503]
101558065  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101558218  [KO:K19558]
101558222  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101558333  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101558490  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
101558664  TNF; tumor necrosis factor [KO:K03156]
101558753  [KO:K04382] [EC:3.1.3.16]
101558979  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
101559130  ZFYVE9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
101559224  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101559341  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
101559352  EMP3; epithelial membrane protein 3 [KO:K26257]
105942724  TGIF2; homeobox protein TGIF2 [KO:K19553]
105943238  AMH; muellerian-inhibiting factor [KO:K04665]
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
sara04010  MAPK signaling pathway
sara04110  Cell cycle
sara04120  Ubiquitin mediated proteolysis
sara04210  Apoptosis
KO pathway
ko04350   

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