KEGG PATHWAY: mmu04350

PATHWAY: mmu04350

Entry

mmu04350 Pathway

Name

TGF-beta signaling pathway - Mus musculus (mouse)

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

mmu04350

TGF-beta signaling pathway

Module

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

Organism

Mus musculus (mouse) [GN:mmu]

Gene

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:2.7.11.30]
110542	Amhr2; anti-Mullerian hormone type 2 receptor [KO:K04672] [EC:2.7.11.30]
21813	Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
11480	Acvr2a; activin receptor IIA [KO:K04670] [EC:2.7.11.30]
11481	Acvr2b; activin receptor IIB [KO:K13596] [EC:2.7.11.30]
12166	Bmpr1a; bone morphogenetic protein receptor, type 1A [KO:K04673] [EC:2.7.11.30]
12167	Bmpr1b; bone morphogenetic protein receptor, type 1B [KO:K13578] [EC:2.7.11.30]
11477	Acvr1; activin A receptor, type 1 [KO:K04675] [EC:2.7.11.30]
21812	Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
11479	Acvr1b; activin A receptor, type 1B [KO:K13567] [EC:2.7.11.30]
269275	Acvr1c; activin A receptor, type IC [KO:K13568] [EC:2.7.11.30]
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:2.3.2.26]
75788	Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
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; retinoblastoma-like 1 (p107) [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:2.3.1.48]
328572	Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
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]
100043674	Rbx1-ps; ring-box 1, pseudogene [KO:K03868]
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:2.7.11.24]
26417	Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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:2.7.11.1]
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:3.1.3.16]
19053	Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
58988	Rps6kb2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
72508	Rps6kb1; ribosomal protein S6 kinase, polypeptide 1 [KO:K04688] [EC:2.7.11.1]

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

KO pathway

ko04350

All links

Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (85)   
   KEGG GENES (85)   
All databases (87)   

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