KEGG   PATHWAY: map04350Help
Entry
map04350                    Pathway                                

Name
TGF-beta signaling pathway
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
09130 Environmental Information Processing; 09132 Signal transduction
BRITE hierarchy
Pathway map
map04350  TGF-beta signaling pathway
map04350

Ortholog table
Module
M00679  BMP signaling [PATH:map04350]
M00680  TGF-beta signaling [PATH:map04350]
M00681  Activin signaling [PATH:map04350]
Disease
H00409  Type II diabetes mellitus
H00430  Fibrodysplasia ossificans progressiva (FOP)
H00431  Ossification of the posterior longitudinal ligament of spine (OPLL)
H00434  Camurati-Engelmann disease
H00466  Grebe dysplasia
H00467  Fibular hypoplasia and complex brachydactyly
H00468  Acromesomelic dysplasia, Demirhan type
H00482  Brachydactyly
H00483  Angel shaped phalangoepiphyseal dysplasia
H00484  Multiple synostosis syndrome
H00533  Hereditary hemorrhagic telangiectasia (HHT)
H00554  Bicuspid aortic valve
H00609  46,XY disorders of sex development (Other)
H00620  Axenfeld-Rieger syndrome (ARS)
H00632  Heterotaxy
H00778  Tarsal-carpal coalition syndrome
H00800  Loeys-Dietz syndrome (LDS)
H00801  Familial thoracic aortic aneurysm and dissection (TAAD)
H00852  Klippel-Feil syndrome(KFS)
H00868  Stapes ankylosis with broad thumb and toes
H00958  Congenital stromal corneal dystrophy (CSCD)
H01023  Juvenile polyposis syndrome
H01024  Hereditary mixed polyposis syndrome
H01027  Anophthalmia and microphthalmia (A/M)
H01075  Peters anomaly
H01149  Ring dermoid of cornea
H01385  Rienhoff syndrome
H01619  Primary pulmonary hypertension (PPH)
H01621  Pulmonary arterial hypertension (PAH)
H02102  Myhre syndrome
Other DBs
GO: 0007179
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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   

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Pathway (3)   
   KEGG MODULE (3)   
Disease (30)   
   KEGG DISEASE (30)   
Gene (122433)   
   KEGG ORTHOLOGY (73)   
   RefGene (122360)   
Literature (14)   
   PubMed (14)   
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