KEGG   PATHWAY: rno04350
rno04350                    Pathway                                

TGF-beta signaling pathway - Rattus norvegicus (rat)
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.
Environmental Information Processing; Signal transduction
Pathway map
rno04350  TGF-beta signaling pathway

Other DBs
GO: 0007179
Rattus norvegicus (rat) [GN:rno]
117275  Chrd; chordin precursor [KO:K04657]
25495  Nog; noggin precursor [KO:K04658]
50594  Nbl1; neuroblastoma suppressor of tumorigenicity 1 precursor [KO:K19558]
289264  Grem2; gremlin-2 precursor [KO:K23318]
50566  Grem1; gremlin-1 precursor [KO:K23318]
445442  Thbs1; thrombospondin-1 precursor [KO:K16857]
29139  Dcn; decorin precursor [KO:K04660]
64507  Fmod; fibromodulin precursor [KO:K08121]
498299  Lefty1; left-right determination factor 1 precursor [KO:K04668]
289316  Lefty2; left-right determination factor 2 precursor [KO:K04668]
24373  Fst; follistatin precursor [KO:K04661]
29373  Bmp2; bone morphogenetic protein 2 precursor [KO:K21283]
25296  Bmp4; bone morphogenetic protein 4 precursor [KO:K04662]
25644  Bmp6; bone morphogenetic protein 6 precursor [KO:K16620]
25196  Inhbb; inhibin beta B chain precursor [KO:K22687]
315824  Bmp5; bone morphogenetic protein 5 precursor [KO:K04663]
85272  Bmp7; bone morphogenetic protein 7 precursor [KO:K16621]
679119  Bmp8b; bone morphogenetic protein 8B isoform X1 [KO:K16622]
680931  Bmp8a; bone morphogenetic protein 8A precursor [KO:K16622]
252835  Gdf5; growth/differentiation factor 5 [KO:K04664]
252834  Gdf6; growth/differentiation factor 6 precursor [KO:K20012]
252833  Gdf7; growth/differentiation factor 7 precursor [KO:K20013]
25378  Amh; muellerian-inhibiting factor precursor [KO:K04665]
315728  Thsd4; thrombospondin type-1 domain-containing protein 4 isoform X1 [KO:K23377]
83727  Fbn1; fibrillin-1 precursor [KO:K06825]
59107  Ltbp1; latent-transforming growth factor beta-binding protein 1 precursor [KO:K19559]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
25717  Tgfb3; transforming growth factor beta-3 proprotein preproprotein [KO:K13377]
29200  Inhba; inhibin beta A chain preproprotein [KO:K04667]
64549  Inhbc; inhibin beta C chain precursor [KO:K22688]
83711  Inhbe; inhibin beta E chain precursor [KO:K22689]
294503  Nodal; nodal homolog precursor [KO:K04666]
81735  Neo1; neogenin isoform X1 [KO:K06766]
310681  Hjv; hemojuvelin precursor [KO:K23100]
81507  Bmpr1a; bone morphogenetic protein receptor type-1A precursor [KO:K04673] [EC:]
310914  Bmpr1b; bone morphogenetic protein receptor type-1B [KO:K13578] [EC:]
79558  Acvr1; activin receptor type-1 precursor [KO:K04675] [EC:]
140590  Bmpr2; bone morphogenetic protein receptor type-2 precursor [KO:K04671] [EC:]
29263  Acvr2a; activin receptor type-2A precursor [KO:K04670] [EC:]
308739  Rgma; repulsive guidance molecule A [KO:K23096]
681433  Rgmb; RGM domain family member B isoform X1 [KO:K06847]
29530  Amhr2; anti-Muellerian hormone type-2 receptor precursor [KO:K04672] [EC:]
29591  Tgfbr1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:]
81810  Tgfbr2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:]
29381  Acvr1b; activin receptor type-1B precursor [KO:K13567] [EC:]
25366  Acvr2b; activin receptor type-2B precursor [KO:K13596] [EC:]
245921  Acvr1c; activin receptor type-1C precursor [KO:K13568] [EC:]
83837  Bambi; BMP and activin membrane-bound inhibitor homolog precursor [KO:K10162]
25671  Smad1; mothers against decapentaplegic homolog 1 [KO:K04676]
59328  Smad5; mothers against decapentaplegic homolog 5 [KO:K16790]
85435  Smad9; mothers against decapentaplegic homolog 9 [KO:K16791]
29357  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
25631  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
50554  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
367100  Smad6; mothers against decapentaplegic homolog 6 [KO:K04677]
81516  Smad7; mothers against decapentaplegic homolog 7 [KO:K19631]
303614  Smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:]
690516  Smurf1; E3 ubiquitin-protein ligase SMURF1 [KO:K04678] [EC:]
313477  Zfyve9; zinc finger FYVE domain-containing protein 9 [KO:K04679]
499508  Zfyve16; zinc finger FYVE domain-containing protein 16 [KO:K04679]
84604  Hamp; hepcidin precursor [KO:K23106]
25261  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
25587  Id2; DNA-binding protein inhibitor ID-2 [KO:K17693]
25585  Id3; DNA-binding protein inhibitor ID-3 [KO:K17694]
291023  Id4; DNA-binding protein inhibitor ID-4 [KO:K17695]
680111  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
116651  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
100360427  E2f4; transcription factor E2F4 [KO:K04682]
361178  Tfdp1; transcription factor Dp-1 [KO:K04683]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:]
170915  Ep300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:]
24790  Sp1; transcription factor Sp1 [KO:K04684]
316742  Tgif1; homeobox protein TGIF1 [KO:K19383]
499929  Tgif2; homeobox protein TGIF2 [KO:K19553]
24577  Myc; myc proto-oncogene protein [KO:K04377]
25164  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
54284  Pitx2; pituitary homeobox 2 isoform 1 [KO:K04686]
300084  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:]
362356  Cul1; cullin-1 [KO:K03347]
287280  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
25712  Ifng; interferon gamma precursor [KO:K04687]
24835  Tnf; tumor necrosis factor [KO:K03156]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:]
Shi Y, Massague J.
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
Cell 113:685-700 (2003)
Derynck R, Zhang YE.
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
Nature 425:577-84 (2003)
Massague J.
How cells read TGF-beta signals.
Nat Rev Mol Cell Biol 1:169-78 (2000)
Siegel PM, Massague J.
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer.
Nat Rev Cancer 3:807-21 (2003)
Shimasaki S, Moore RK, Otsuka F, Erickson GF.
The bone morphogenetic protein system in mammalian reproduction.
Endocr Rev 25:72-101 (2004)
De Robertis EM, Larrain J, Oelgeschlager M, Wessely O.
The establishment of Spemann's organizer and patterning of the vertebrate embryo.
Nat Rev Genet 1:171-81 (2000)
Gumienny TL, Padgett RW.
The other side of TGF-beta superfamily signal regulation: thinking outside the cell.
Trends Endocrinol Metab 13:295-9 (2002)
Hamada H, Meno C, Watanabe D, Saijoh Y.
Establishment of vertebrate left-right asymmetry.
Nat Rev Genet 3:103-13 (2002)
Chang H, Brown CW, Matzuk MM.
Genetic analysis of the mammalian transforming growth factor-beta superfamily.
Endocr Rev 23:787-823 (2002)
Morita K, Chow KL, Ueno N.
Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family.
Development 126:1337-47 (1999)
Krishna S, Maduzia LL, Padgett RW.
Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans.
Development 126:251-60 (1999)
Chen Y, Mironova E, Whitaker LL, Edwards L, Yost HJ, Ramsdell AF.
ALK4 functions as a receptor for multiple TGF beta-related ligands to regulate left-right axis determination and mesoderm induction in Xenopus.
Dev Biol 268:280-94 (2004)
Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massague J, Niehrs C
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
Nature 401:480-5 (1999)
Yan X, Lin Z, Chen F, Zhao X, Chen H, Ning Y, Chen YG
Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling.
J Biol Chem 284:30097-104 (2009)
Hildebrand A, Romaris M, Rasmussen LM, Heinegard D, Twardzik DR, Border WA, Ruoslahti E
Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.
Biochem J 302 ( Pt 2):527-34 (1994)
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
Differential expression of fibromodulin, a transforming growth factor-beta modulator, in fetal skin development and scarless repair.
Am J Pathol 157:423-33 (2000)
Anderson GJ, Frazer DM
Iron metabolism meets signal transduction.
Nat Genet 38:503-4 (2006)
Canali S, Core AB, Zumbrennen-Bullough KB, Merkulova M, Wang CY, Schneyer AL, Pietrangelo A, Babitt JL
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.
Endocrinology 157:1146-62 (2016)
Ganz T, Nemeth E
Iron homeostasis in host defence and inflammation.
Nat Rev Immunol 15:500-10 (2015)
Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, Lin HY
Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor.
J Biol Chem 280:29820-7 (2005)
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
DRAGON, a bone morphogenetic protein co-receptor.
J Biol Chem 280:14122-9 (2005)
rno04010  MAPK signaling pathway
rno04110  Cell cycle
rno04120  Ubiquitin mediated proteolysis
rno04210  Apoptosis
KO pathway

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