Entry
Name
TGF-beta signaling pathway - Danio rerio (zebrafish)
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
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Danio rerio (zebrafish) [GN:
dre ]
Gene
404629 nbl1; neuroblastoma suppressor of tumorigenicity 1 precursor [KO:K19558 ]
30632 bmp2b; bone morphogenetic protein 2b precursor [KO:K21283 ]
140619 admp; anti-dorsalizing morphogenic protein precursor [KO:K21283 ]
30631 bmp2a; bone morphogenetic protein 2 precursor [KO:K21283 ]
30612 bmp4; bone morphogenetic protein 4 precursor [KO:K04662 ]
503761 bmp6; bone morphogenetic protein 6 precursor [KO:K16620 ]
30275 inhbb; inhibin beta B chain precursor [KO:K22687 ]
394026 bmp5; bone morphogenetic protein 5 precursor [KO:K04663 ]
30584 bmp7a; bone morphogenetic protein 7a precursor [KO:K16621 ]
566470 gdf6a; growth/differentiation factor 6-A precursor [KO:K20012 ]
30180 gdf6b; growth/differentiation factor 6-B precursor [KO:K20012 ]
30642 gdf7; growth/differentiation factor 6-A [KO:K20013 ]
493624 amh; muellerian-inhibiting factor precursor [KO:K04665 ]
405785 tnfa; tumor necrosis factor a (TNF superfamily, member 2) [KO:K03156 ]
556634 adamtsl7; thrombospondin type-1 domain-containing protein 4 [KO:K23377 ]
562072 ltbp1; latent-transforming growth factor beta-binding protein 1 isoform X1 [KO:K19559 ]
359834 tgfb1a; transforming growth factor, beta 1a precursor [KO:K13375 ]
563884 tgfb1b; transforming growth factor beta-1 [KO:K13375 ]
369194 tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376 ]
559723 tgfb2l; transforming growth factor beta-2-like [KO:K13376 ]
369195 tgfb3; transforming growth factor beta-3 proprotein precursor [KO:K13377 ]
553816 inhbab; inhibin subunit beta Ab precursor [KO:K04667 ]
321842 rgmd; RGM domain family, member D precursor [KO:K23096 ]
414273 rgmb; RGM domain family member B precursor [KO:K06847 ]
796607 si:dkey-264d12.4; epithelial membrane protein 3-like [KO:K26257 ]
560722 emp3b; epithelial membrane protein 3b (MAM blood group) precursor [KO:K26257 ]
445318 nrros; transforming growth factor beta activator LRRC33 precursor [KO:K26317 ]
83496 bambia; BMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a precursor [KO:K10162 ]
431736 bambib; BMP and activin membrane-bound inhibitor homolog (Xenopus laevis) b precursor [KO:K10162 ]
30628 smad1; mothers against decapentaplegic homolog 1 [KO:K04676 ]
30641 smad5; mothers against decapentaplegic homolog 5 [KO:K16790 ]
445564 smad9; mothers against decapentaplegic homolog 9 [KO:K16791 ]
30639 smad2; mothers against decapentaplegic homolog 2 [KO:K04500 ]
326283 smad3b; mothers against decapentaplegic homolog 3b [KO:K23605 ]
58092 smad3a; mothers against decapentaplegic homolog 3a [KO:K23605 ]
560317 smad10a; uncharacterized protein LOC560317 isoform 2 [KO:K04501 ]
559111 smad4a; mothers against decapentaplegic homolog 4a [KO:K04501 ]
100151181 si:dkey-239n17.4; mothers against decapentaplegic homolog 4-like [KO:K04501 ]
794669 gb:cr929477; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501 ]
564395 smad6b; mothers against decapentaplegic homolog 6b [KO:K04677 ]
116992 smad6a; mothers against decapentaplegic homolog 6a [KO:K04677 ]
326282 smad7; mothers against decapentaplegic homolog 7 [KO:K19631 ]
100005449 zfyve9a; zinc finger FYVE domain-containing protein 9 isoform X2 [KO:K04679 ]
794689 zfyve16; zinc finger FYVE domain-containing protein 16 isoform X2 [KO:K04679 ]
101882992 zfyve9b; zinc finger FYVE domain-containing protein 9 [KO:K04679 ]
393716 skp1; S-phase kinase-associated protein 1 [KO:K03094 ]
406411 rhoaa; rho-related GTP-binding protein RhoA-A [KO:K04513 ]
406659 rhoac; rho-related GTP-binding protein RhoA-C [KO:K04513 ]
436718 rhocb; rho-related GTP-binding protein RhoA-D [KO:K04513 ]
751630 zgc:153713; RhoA_like domain-containing protein [KO:K04513 ]
406685 ppp2r1ba; protein phosphatase 2, regulatory subunit A, beta a [KO:K03456 ]
449548 ppp2r1bb; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456 ]
393885 ppp2cab; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382 ] [EC:3.1.3.16 ]
406582 ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382 ] [EC:3.1.3.16 ]
402837 hamp; hepcidin-1 precursor isoform 1 precursor [KO:K23106 ]
30493 id1; DNA-binding protein inhibitor ID-1 [KO:K04680 ]
266599 id2a; DNA-binding protein inhibitor ID-2a [KO:K17693 ]
321364 id2b; DNA-binding protein inhibitor ID-2b [KO:K17693 ]
402908 e2f5; transcription factor E2F5 isoform 1 [KO:K04682 ]
30101 skia; v-ski avian sarcoma viral oncogene homolog a [KO:K26503 ]
30113 skib; v-ski avian sarcoma viral oncogene homolog b [KO:K26503 ]
563090 sin3aa; SIN3 transcription regulator family member Aa [KO:K11644 ]
323346 sin3ab; paired amphipathic helix protein Sin3a isoform X2 [KO:K11644 ]
30686 myca; transcriptional regulator Myc-A [KO:K04377 ]
Compound
Reference
Authors
Shi Y, Massague J.
Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
Journal
Reference
Authors
Derynck R, Zhang YE.
Title
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
Journal
Reference
Authors
Massague J.
Title
How cells read TGF-beta signals.
Journal
Reference
Authors
Siegel PM, Massague J.
Title
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
Journal
Reference
Authors
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
Title
The bone morphogenetic protein system in mammalian reproduction.
Journal
Reference
Authors
De Robertis EM, Larrain J, Oelgeschlager M, Wessely O.
Title
The establishment of Spemann's organizer and patterning of the vertebrate embryo.
Journal
Reference
Authors
Gumienny TL, Padgett RW.
Title
The other side of TGF-beta superfamily signal regulation: thinking outside the cell.
Journal
Reference
Authors
Hamada H, Meno C, Watanabe D, Saijoh Y.
Title
Establishment of vertebrate left-right asymmetry.
Journal
Reference
Authors
Chang H, Brown CW, Matzuk MM.
Title
Genetic analysis of the mammalian transforming growth factor-beta superfamily.
Journal
Reference
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
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
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
Authors
Anderson GJ, Frazer DM
Title
Iron metabolism meets signal transduction.
Journal
Reference
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
Reference
Authors
Ganz T, Nemeth E
Title
Iron homeostasis in host defence and inflammation.
Journal
Reference
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
Reference
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
Reference
Authors
Vogt AS, Arsiwala T, Mohsen M, Vogel M, Manolova V, Bachmann MF
Title
On Iron Metabolism and Its Regulation.
Journal
Reference
Authors
Ikushima H, Miyazono K
Title
TGFbeta signalling: a complex web in cancer progression.
Journal
Related pathway
KO pathway
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