KEGG   PATHWAY: mmu04350
Entry
mmu04350                    Pathway                                
Name
TGF-beta signaling pathway - Mus musculus (house 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
mmu04350

Other DBs
GO: 0007179
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
104394  E2f4; E2F transcription factor 4 [KO:K04682]
110542  Amhr2; anti-Mullerian hormone type 2 receptor [KO:K04672] [EC:2.7.11.30]
11477  Acvr1; activin A receptor, type 1 [KO:K04675] [EC:2.7.11.30]
11479  Acvr1b; activin A receptor, type 1B [KO:K13567] [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]
11705  Amh; anti-Mullerian hormone [KO:K04665]
11848  Rhoa; ras homolog family member A [KO:K04513]
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]
12163  Bmp8a; bone morphogenetic protein 8a [KO:K16622]
12164  Bmp8b; bone morphogenetic protein 8b [KO:K16622]
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]
12168  Bmpr2; bone morphogenetic protein receptor type 2 [KO:K04671] [EC:2.7.11.30]
12579  Cdkn2b; cyclin dependent kinase inhibitor 2B [KO:K04685]
12667  Chrd; chordin [KO:K04657]
12914  Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
13179  Dcn; decorin [KO:K04660]
13559  E2f5; E2F transcription factor 5 [KO:K04682]
13590  Lefty1; left right determination factor 1 [KO:K04668]
13732  Emp3; epithelial membrane protein 3 [KO:K26257]
14118  Fbn1; fibrillin 1 [KO:K06825]
14264  Fmod; fibromodulin [KO:K08121]
14313  Fst; follistatin [KO:K04661]
14563  Gdf5; growth differentiation factor 5 [KO:K04664]
15182  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
15216  Hfe; homeostatic iron regulator [KO:K26535]
15901  Id1; inhibitor of DNA binding 1, HLH protein [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]
15978  Ifng; interferon gamma [KO:K04687]
16323  Inhba; inhibin beta-A [KO:K04667]
16324  Inhbb; inhibin beta-B [KO:K22687]
16325  Inhbc; inhibin beta-C [KO:K22688]
16326  Inhbe; inhibin beta-E [KO:K22689]
17125  Smad1; SMAD family member 1 [KO:K04676]
17126  Smad2; SMAD family member 2 [KO:K04500]
17127  Smad3; SMAD family member 3 [KO:K23605]
17128  Smad4; SMAD family member 4 [KO:K04501]
17129  Smad5; SMAD family member 5 [KO:K16790]
17130  Smad6; SMAD family member 6 [KO:K04677]
17131  Smad7; SMAD family member 7 [KO:K19631]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
17965  Nbl1; NBL1, DAN family BMP antagonist [KO:K19558]
18007  Neo1; neogenin [KO:K06766]
18119  Nodal; nodal growth differentiation factor [KO:K04666]
18121  Nog; noggin [KO:K04658]
18741  Pitx2; paired-like homeodomain transcription factor 2 [KO:K04686]
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]
19650  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
19877  Rock1; Rho-associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
20185  Ncor1; nuclear receptor co-repressor 1 [KO:K04650]
20466  Sin3a; transcriptional regulator, SIN3A (yeast) [KO:K11644]
20481  Ski; ski sarcoma viral oncogene homolog (avian) [KO:K26503]
20482  Skil; SKI-like [KO:K18499]
20683  Sp1; trans-acting transcription factor 1 [KO:K04684]
207596  Thsd4; thrombospondin, type I, domain containing 4 [KO:K23377]
209268  Igsf1; immunoglobulin superfamily, member 1 [KO:K26168]
21402  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
21781  Tfdp1; transcription factor Dp 1 [KO:K04683]
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]
21812  Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
21815  Tgif1; TGFB-induced factor homeobox 1 [KO:K19383]
21825  Thbs1; thrombospondin 1 [KO:K16857]
218441  Zfyve16; zinc finger, FYVE domain containing 16 [KO:K04679]
21926  Tnf; tumor necrosis factor [KO:K03156]
22041  Trf; transferrin [KO:K14736]
22042  Tfrc; transferrin receptor [KO:K06503]
224109  Nrros; negative regulator of reactive oxygen species [KO:K26317]
228839  Tgif2; TGFB-induced factor homeobox 2 [KO:K19553]
230597  Zfyve9; zinc finger, FYVE domain containing 9 [KO:K04679]
238057  Gdf7; growth differentiation factor 7 [KO:K20013]
23892  Grem1; gremlin 1, DAN family BMP antagonist [KO:K23318]
23893  Grem2; gremlin 2, DAN family BMP antagonist [KO:K23318]
242316  Gdf6; growth differentiation factor 6 [KO:K20012]
244058  Rgma; repulsive guidance molecule family member A [KO:K23096]
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]
268977  Ltbp1; latent transforming growth factor beta binding protein 1 [KO:K19559]
269275  Acvr1c; activin A receptor, type IC [KO:K13568] [EC:2.7.11.30]
26965  Cul1; cullin 1 [KO:K03347]
320202  Lefty2; left-right determination factor 2 [KO:K04668]
328572  Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
380664  Lemd3; LEM domain containing 3 [KO:K19410]
433759  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
434215  Lrrc32; leucine rich repeat containing 32 [KO:K26316]
50765  Tfr2; transferrin receptor 2 [KO:K23910]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
55994  Smad9; SMAD family member 9 [KO:K16791]
56438  Rbx1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
58988  Rps6kb2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
66313  Smurf2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:2.3.2.26]
66438  Hamp2; hepcidin antimicrobial peptide 2 [KO:K23106]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
68010  Bambi; BMP and activin membrane-bound inhibitor [KO:K10162]
68777  Tmem53; transmembrane protein 53 [KO:K28359]
68799  Rgmb; repulsive guidance molecule family member B [KO:K06847]
69585  Hjv; hemojuvelin BMP co-receptor [KO:K23100]
71775  Inhca; inhibitor of carbonic anhydrase [KO:K14736]
72508  Rps6kb1; ribosomal protein S6 kinase, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
75788  Smurf1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:2.3.2.26]
84506  Hamp; hepcidin antimicrobial peptide [KO:K23106]
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
mmu04010  MAPK signaling pathway
mmu04110  Cell cycle
mmu04120  Ubiquitin mediated proteolysis
mmu04210  Apoptosis
KO pathway
ko04350   

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