KEGG   PATHWAY: mlk04350
Entry
mlk04350                    Pathway                                
Name
TGF-beta signaling pathway - Mustela lutreola (European mink)
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
mlk04350  TGF-beta signaling pathway
mlk04350

Other DBs
GO: 0007179
Organism
Mustela lutreola (European mink) [GN:mlk]
Gene
131807320  GDF7; growth/differentiation factor 7 [KO:K20013]
131807411  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
131807639  BMP7; bone morphogenetic protein 7 isoform X1 [KO:K16621]
131807713  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
131807731  TGIF2; homeobox protein TGIF2 [KO:K19553]
131807958  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
131808045  BMP2; bone morphogenetic protein 2 [KO:K21283]
131808060  GDF5; growth/differentiation factor 5 [KO:K04664]
131809045  TMEM53; transmembrane protein 53 [KO:K28359]
131809139  BMP8B; bone morphogenetic protein 8B isoform X1 [KO:K16622]
131809175  SKI; ski oncogene isoform X1 [KO:K26503]
131809310  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
131809397  BMP8A; bone morphogenetic protein 8A isoform X1 [KO:K16622]
131809427  NBL1; neuroblastoma suppressor of tumorigenicity 1 [KO:K19558]
131809627  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
131809893  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
131810150  HJV; hemojuvelin [KO:K23100]
131810886  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
131811075  SMAD7; mothers against decapentaplegic homolog 7 [KO:K19631]
131811411  TGIF1; homeobox protein TGIF1 [KO:K19383]
131811641  [KO:K04513]
131811758  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
131811851  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
131811852  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
131812377  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
131812650  CDKN2B; cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
131813510  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
131813560  SMAD9; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 9 [KO:K16791]
131814377  GREM2; gremlin-2 isoform X1 [KO:K23318]
131814771  [KO:K04668]
131815106  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
131815140  FMOD; fibromodulin [KO:K08121]
131816533  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
131816662  NOG; noggin [KO:K04658]
131816856  NCOR1; nuclear receptor corepressor 1 isoform X1 [KO:K04650]
131816894  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
131816965  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
131817361  HAMP; hepcidin [KO:K23106]
131817379  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
131817494  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
131817900  E2F4; transcription factor E2F4 [KO:K04682]
131818450  EMP3; epithelial membrane protein 3 [KO:K26257]
131819609  TFR2; transferrin receptor protein 2 isoform X1 [KO:K23910]
131819828  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
131820095  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
131820131  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
131820528  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
131821900  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
131823235  AMH; muellerian-inhibiting factor [KO:K04665]
131823928  RHOA; transforming protein RhoA [KO:K04513]
131824361  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
131824456  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
131824554  [KO:K14736]
131824556  [KO:K14736]
131824666  TFRC; transferrin receptor protein 1 isoform X1 [KO:K06503]
131824680  NRROS; transforming growth factor beta activator LRRC33 isoform X1 [KO:K26317]
131824783  CHRD; chordin isoform X1 [KO:K04657]
131824875  SKIL; ski-like protein isoform X1 [KO:K18499]
131826401  MYC; myc proto-oncogene protein [KO:K04377]
131826581  GDF6; growth/differentiation factor 6 [KO:K20012]
131826646  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
131826915  INHBB; inhibin beta B chain [KO:K22687]
131826989  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
131827196  ACVR1; activin receptor type-1 isoform X1 [KO:K04675] [EC:2.7.11.30]
131827199  ACVR1C; activin receptor type-1C [KO:K13568] [EC:2.7.11.30]
131827560  BMPR2; bone morphogenetic protein receptor type-2 isoform X1 [KO:K04671] [EC:2.7.11.30]
131827695  [KO:K03094]
131828743  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
131829137  INHBA; inhibin beta A chain [KO:K04667]
131829277  PITX2; pituitary homeobox 2 isoform X1 [KO:K04686]
131829905  CUL1; cullin-1 [KO:K03347]
131830232  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
131830323  NODAL; nodal homolog [KO:K04666]
131831732  FST; follistatin isoform X1 [KO:K04661]
131832040  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
131832073  SMAD5; mothers against decapentaplegic homolog 5 [KO:K16790]
131832405  ZFYVE16; zinc finger FYVE domain-containing protein 16 isoform X1 [KO:K04679]
131832491  RGMB; repulsive guidance molecule B [KO:K06847]
131832822  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
131832965  HFE; hereditary hemochromatosis protein isoform X1 [KO:K26535]
131833482  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
131834122  BMP5; bone morphogenetic protein 5 isoform X1 [KO:K04663]
131834372  TNF; tumor necrosis factor isoform X1 [KO:K03156]
131834506  BMP6; bone morphogenetic protein 6 [KO:K16620]
131834794  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
131835648  RGMA; repulsive guidance molecule A [KO:K23096]
131835759  SIN3A; paired amphipathic helix protein Sin3a isoform X1 [KO:K11644]
131835761  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
131835803  NEO1; neogenin isoform X1 [KO:K06766]
131835830  THSD4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
131835962  SMAD6; mothers against decapentaplegic homolog 6 isoform X1 [KO:K04677]
131835965  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
131836071  GREM1; gremlin-1 isoform X1 [KO:K23318]
131836095  THBS1; thrombospondin-1 [KO:K16857]
131836250  FBN1; fibrillin-1 [KO:K06825]
131836584  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
131836852  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
131838115  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
131838561  INHBC; inhibin beta C chain [KO:K22688]
131838562  INHBE; inhibin beta E chain [KO:K22689]
131838693  AMHR2; anti-Muellerian hormone type-2 receptor [KO:K04672] [EC:2.7.11.30]
131838694  SP1; transcription factor Sp1 [KO:K04684]
131838744  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
131839108  LEMD3; inner nuclear membrane protein Man1 [KO:K19410]
131839127  IFNG; interferon gamma [KO:K04687]
131839253  DCN; decorin [KO:K04660]
131839520  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
131839523  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
131840439  LRRC32; transforming growth factor beta activator LRRC32 [KO:K26316]
131840529  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
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
mlk04010  MAPK signaling pathway
mlk04110  Cell cycle
mlk04120  Ubiquitin mediated proteolysis
mlk04210  Apoptosis
KO pathway
ko04350   

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