KEGG   PATHWAY: lav04350
Entry
lav04350                    Pathway                                
Name
TGF-beta signaling pathway - Loxodonta africana (African savanna elephant)
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
lav04350  TGF-beta signaling pathway
lav04350

Other DBs
GO: 0007179
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100653832  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
100653946  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
100654115  BMP4; bone morphogenetic protein 4 isoform X1 [KO:K04662]
100654281  ACVR1B; activin receptor type-1B isoform X1 [KO:K13567] [EC:2.7.11.30]
100654486  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100654870  NODAL; nodal homolog [KO:K04666]
100654878  BMP2; bone morphogenetic protein 2 [KO:K21283]
100654982  ZFYVE9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
100655364  ID1; DNA-binding protein inhibitor ID-1 [KO:K04680]
100655443  FMOD; fibromodulin [KO:K08121]
100656026  SIN3A; LOW QUALITY PROTEIN: paired amphipathic helix protein Sin3a [KO:K11644]
100656286  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100656534  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100656988  ID4; DNA-binding protein inhibitor ID-4 [KO:K17695]
100657000  GREM1; gremlin-1 [KO:K23318]
100657418  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.39]
100657479  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100657709  INHBA; inhibin beta A chain [KO:K04667]
100658031  ACVR2B; LOW QUALITY PROTEIN: activin receptor type-2B [KO:K13596] [EC:2.7.11.30]
100658075  DCN; decorin [KO:K04660]
100658220  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100658507  TMEM53; transmembrane protein 53 isoform X1 [KO:K28359]
100658525  HAMP; hepcidin [KO:K23106]
100658600  E2F4; transcription factor E2F4 [KO:K04682]
100658874  BMP8A; bone morphogenetic protein 8A [KO:K16622]
100659407  EMP3; epithelial membrane protein 3 [KO:K26257]
100659509  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100659642  [KO:K23377]
100660171  TGIF1; homeobox protein TGIF1 [KO:K19383]
100660194  BMPR1B; bone morphogenetic protein receptor type-1B isoform X1 [KO:K13578] [EC:2.7.11.30]
100661096  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100661343  PITX2; LOW QUALITY PROTEIN: pituitary homeobox 2 [KO:K04686]
100661600  BMPR2; LOW QUALITY PROTEIN: bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
100661935  SKIL; ski-like protein isoform X1 [KO:K18499]
100661991  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
100662123  NOG; noggin [KO:K04658]
100662507  HFE; hereditary hemochromatosis protein isoform X3 [KO:K26535]
100662543  SP1; transcription factor Sp1 [KO:K04684]
100662666  BAMBI; BMP and activin membrane-bound inhibitor homolog isoform X1 [KO:K10162]
100662668  [KO:K04668]
100662671  ID2; DNA-binding protein inhibitor ID-2 [KO:K17693]
100662698  IGSF1; immunoglobulin superfamily member 1 [KO:K26168]
100662773  NEO1; neogenin [KO:K06766]
100662817  AMHR2; anti-Muellerian hormone type-2 receptor isoform X1 [KO:K04672] [EC:2.7.11.30]
100663178  [KO:K14736]
100663285  IFNG; interferon gamma [KO:K04687]
100663335  CHRD; LOW QUALITY PROTEIN: chordin [KO:K04657]
100663461  [KO:K14736]
100663495  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100663532  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100663731  [KO:K04498] [EC:2.3.1.48]
100663845  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100664027  LRRC32; leucine-rich repeat-containing protein 32 [KO:K26316]
100664132  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100664600  CUL1; cullin-1 [KO:K03347]
100664726  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100664950  NRROS; negative regulator of reactive oxygen species [KO:K26317]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100665401  GDF7; LOW QUALITY PROTEIN: growth/differentiation factor 7 [KO:K20013]
100665588  FST; follistatin isoform X1 [KO:K04661]
100665874  MYC; myc proto-oncogene protein [KO:K04377]
100666098  ID3; DNA-binding protein inhibitor ID-3 [KO:K17694]
100666202  SMURF2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
100666443  ZFYVE16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
100666483  SMURF1; E3 ubiquitin-protein ligase SMURF1 isoform X2 [KO:K04678] [EC:2.3.2.26]
100666495  BMP7; bone morphogenetic protein 7 [KO:K16621]
100666676  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
100666694  BMP5; bone morphogenetic protein 5 [KO:K04663]
100666845  HDAC1; histone deacetylase 1 isoform X2 [KO:K06067] [EC:3.5.1.98]
100666895  LEMD3; LOW QUALITY PROTEIN: inner nuclear membrane protein Man1 [KO:K19410]
100666899  ACVR1; activin receptor type-1 isoform X2 [KO:K04675] [EC:2.7.11.30]
100667186  ACVR1C; activin receptor type-1C isoform X2 [KO:K13568] [EC:2.7.11.30]
100667228  TFRC; transferrin receptor protein 1 [KO:K06503]
100667424  SMAD1; mothers against decapentaplegic homolog 1 [KO:K04676]
100667431  THBS1; thrombospondin-1 [KO:K16857]
100667497  GREM2; gremlin-2 [KO:K23318]
100667634  TGFB1; transforming growth factor beta-1 [KO:K13375]
100667927  SMAD5; mothers against decapentaplegic homolog 5 isoform X1 [KO:K16790]
100668255  GDF5; growth/differentiation factor 5 [KO:K04664]
100668461  RGMA; repulsive guidance molecule A [KO:K23096]
100668483  SMAD6; mothers against decapentaplegic homolog 6 [KO:K04677]
100669652  GDF6; growth/differentiation factor 6 [KO:K20012]
100669709  NCOR1; LOW QUALITY PROTEIN: nuclear receptor corepressor 1 [KO:K04650]
100669718  HFE2; hemojuvelin isoform X1 [KO:K23100]
100670539  [KO:K16622]
100671034  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
100671392  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
100671397  INHBB; inhibin beta B chain [KO:K22687]
100672302  ACVR2A; activin receptor type-2A isoform X1 [KO:K04670] [EC:2.7.11.30]
100672839  BMP6; LOW QUALITY PROTEIN: bone morphogenetic protein 6 [KO:K16620]
100673003  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100673185  LEFTY2; left-right determination factor 2 isoform X1 [KO:K04668]
100673199  [KO:K19558]
100673540  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100675136  FBN1; fibrillin-1 [KO:K06825]
100675217  LTBP1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559]
100676230  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100676233  SKI; ski oncogene [KO:K26503]
100676711  SMAD9; mothers against decapentaplegic homolog 9 isoform X1 [KO:K16791]
100677125  TNF; tumor necrosis factor isoform X2 [KO:K03156]
100677411  [KO:K23910]
100677416  INHBC; inhibin beta C chain [KO:K22688]
100677447  RHOA; transforming protein RhoA [KO:K04513]
100677702  INHBE; inhibin beta E chain [KO:K22689]
104845389  TGIF2; homeobox protein TGIF2 [KO:K19553]
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
lav04010  MAPK signaling pathway
lav04110  Cell cycle
lav04120  Ubiquitin mediated proteolysis
lav04210  Apoptosis
KO pathway
ko04350   

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