KEGG   PATHWAY: mmu04350Help
mmu04350                    Pathway                                

TGF-beta signaling pathway - Mus musculus (mouse)
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
BRITE hierarchy
Pathway map
mmu04350  TGF-beta signaling pathway

Ortholog table
mmu_M00679  BMP signaling [PATH:mmu04350]
mmu_M00680  TGF-beta signaling [PATH:mmu04350]
mmu_M00681  Activin signaling [PATH:mmu04350]
Other DBs
BSID: 83261
GO: 0007179
Mus musculus (mouse) [GN:mmu]
12667  Chrd; chordin [KO:K04657]
18121  Nog; noggin [KO:K04658]
17965  Nbl1; neuroblastoma, suppression of tumorigenicity 1 [KO:K19558]
21825  Thbs1; thrombospondin 1 [KO:K16857]
13179  Dcn; decorin [KO:K04660]
13590  Lefty1; left right determination factor 1 [KO:K04668]
320202  Lefty2; left-right determination factor 2 [KO:K04668]
14313  Fst; follistatin [KO:K04661]
12156  Bmp2; bone morphogenetic protein 2 [KO:K21283]
12159  Bmp4; bone morphogenetic protein 4 [KO:K04662]
12160  Bmp5; bone morphogenetic protein 5 [KO:K04663]
12161  Bmp6; bone morphogenetic protein 6 [KO:K16620]
12162  Bmp7; bone morphogenetic protein 7 [KO:K16621]
12164  Bmp8b; bone morphogenetic protein 8b [KO:K16622]
12163  Bmp8a; bone morphogenetic protein 8a [KO:K16622]
14563  Gdf5; growth differentiation factor 5 [KO:K04664]
242316  Gdf6; growth differentiation factor 6 [KO:K20012]
238057  Gdf7; growth differentiation factor 7 [KO:K20013]
11705  Amh; anti-Mullerian hormone [KO:K04665]
268977  Ltbp1; latent transforming growth factor beta binding protein 1 [KO:K19559]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21809  Tgfb3; transforming growth factor, beta 3 [KO:K13377]
16323  Inhba; inhibin beta-A [KO:K04667]
16324  Inhbb; inhibin beta-B [KO:K04667]
16325  Inhbc; inhibin beta-C [KO:K04667]
16326  Inhbe; inhibin beta-E [KO:K04667]
18119  Nodal; nodal [KO:K04666]
12168  Bmpr2; bone morphogenetic protein receptor, type II (serine/threonine kinase) [KO:K04671] [EC:]
110542  Amhr2; anti-Mullerian hormone type 2 receptor [KO:K04672] [EC:]
21813  Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:]
11481  Acvr2b; activin receptor IIB [KO:K13596] [EC:]
11480  Acvr2a; activin receptor IIA [KO:K13596] [EC:]
12166  Bmpr1a; bone morphogenetic protein receptor, type 1A [KO:K04673] [EC:]
12167  Bmpr1b; bone morphogenetic protein receptor, type 1B [KO:K13578] [EC:]
11477  Acvr1; activin A receptor, type 1 [KO:K04675] [EC:]
21812  Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:]
11479  Acvr1b; activin A receptor, type 1B [KO:K13567] [EC:]
269275  Acvr1c; activin A receptor, type IC [KO:K13568] [EC:]
68010  Bambi; BMP and activin membrane-bound inhibitor [KO:K10162]
17125  Smad1; SMAD family member 1 [KO:K04676]
17129  Smad5; SMAD family member 5 [KO:K16790]
55994  Smad9; SMAD family member 9 [KO:K16791]
17126  Smad2; SMAD family member 2 [KO:K04500]
17127  Smad3; SMAD family member 3 [KO:K04500]
17128  Smad4; SMAD family member 4 [KO:K04501]
17130  Smad6; SMAD family member 6 [KO:K04677]
17131  Smad7; SMAD family member 7 [KO:K19631]
66313  Smurf2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:]
75788  Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:]
218441  Zfyve16; zinc finger, FYVE domain containing 16 [KO:K04679]
230597  Zfyve9; zinc finger, FYVE domain containing 9 [KO:K04679]
15901  Id1; inhibitor of DNA binding 1 [KO:K04680]
15902  Id2; inhibitor of DNA binding 2 [KO:K17693]
15903  Id3; inhibitor of DNA binding 3 [KO:K17694]
15904  Id4; inhibitor of DNA binding 4 [KO:K17695]
19650  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
104394  E2f4; E2F transcription factor 4 [KO:K04682]
13559  E2f5; E2F transcription factor 5 [KO:K04682]
21781  Tfdp1; transcription factor Dp 1 [KO:K04683]
12914  Crebbp; CREB binding protein [KO:K04498] [EC:]
328572  Ep300; E1A binding protein p300 [KO:K04498] [EC:]
20683  Sp1; trans-acting transcription factor 1 [KO:K04684]
21815  Tgif1; TGFB-induced factor homeobox 1 [KO:K19383]
228839  Tgif2; TGFB-induced factor homeobox 2 [KO:K19553]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
12579  Cdkn2b; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
18741  Pitx2; paired-like homeodomain transcription factor 2 [KO:K04686]
56438  Rbx1; ring-box 1 [KO:K03868] [EC:]
26965  Cul1; cullin 1 [KO:K03347]
21402  Skp1a; S-phase kinase-associated protein 1A [KO:K03094]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
15978  Ifng; interferon gamma [KO:K04687]
21926  Tnf; tumor necrosis factor [KO:K03156]
11848  Rhoa; ras homolog family member A [KO:K04513]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
19877  Rock1; Rho-associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:]
58988  Rps6kb2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04688] [EC:]
72508  Rps6kb1; ribosomal protein S6 kinase, polypeptide 1 [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)
KO pathway

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