KEGG   PATHWAY: hsa04350Help
Entry
hsa04350                    Pathway                                

Name
TGF-beta signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
TGF-beta signaling pathway
hsa04350

All organismsOrtholog table
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 with genital anomalies
H00482  
Brachydactyly
H00483  
Brachydactyly
H00484  
Other brachydactylies
H00533  
Hereditary hemorrhagic telangiectasia (HHT)
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
H01300  
Primary pulmonary hypertension (PPH)
Drug
D00742  
Etanercept (genetical recombination) (JAN)
D02597  
Adalimumab (genetical recombination) (JAN)
D02598  
Infliximab (genetical recombination) (JAN)
D03441  
Certolizumab pegol (genetical recombination) (JAN)
D04358  
Golimumab (genetical recombination) (JAN)
D05146  
Nerelimomab (USAN/INN)
D05263  
Onercept (USAN/INN)
D05393  
Pegsunercept (USAN)
D07436  
Afelimomab (INN)
D09014  
Terameprocol (INN/USAN)
D09620  
Fresolimumab (USAN/INN)
D09670  
Sotatercept (USAN/INN)
D09944  
Ozoralizumab (USAN)
D10437  
Galunisertib (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
8646  
CHRD; chordin [KO:K04657]
9241  
NOG; noggin [KO:K04658]
7057  
THBS1; thrombospondin 1 [KO:K16857]
1634  
DCN; decorin [KO:K04660]
10637  
LEFTY1; left-right determination factor 1 [KO:K04668]
7044  
LEFTY2; left-right determination factor 2 [KO:K04668]
10468  
FST; follistatin [KO:K04661]
650  
BMP2; bone morphogenetic protein 2 [KO:K04662]
652  
BMP4; bone morphogenetic protein 4 [KO:K04662]
653  
BMP5; bone morphogenetic protein 5 [KO:K04663]
654  
BMP6; bone morphogenetic protein 6 [KO:K16620]
655  
BMP7; bone morphogenetic protein 7 [KO:K16621]
656  
BMP8B; bone morphogenetic protein 8b [KO:K16622]
353500  
BMP8A; bone morphogenetic protein 8a [KO:K16622]
151449  
GDF7; growth differentiation factor 7 [KO:K04664]
8200  
GDF5; growth differentiation factor 5 [KO:K04664]
392255  
GDF6; growth differentiation factor 6 [KO:K04664]
268  
AMH; anti-Mullerian hormone [KO:K04665]
7040  
TGFB1; transforming growth factor, beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor, beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor, beta 3 [KO:K13377]
3624  
INHBA; inhibin, beta A [KO:K04667]
3625  
INHBB; inhibin, beta B [KO:K04667]
3626  
INHBC; inhibin, beta C [KO:K04667]
83729  
INHBE; inhibin, beta E [KO:K04667]
4838  
NODAL; nodal growth differentiation factor [KO:K04666]
659  
BMPR2; bone morphogenetic protein receptor, type II (serine/threonine kinase) [KO:K04671] [EC:2.7.11.30]
269  
AMHR2; anti-Mullerian hormone receptor, type II [KO:K04672] [EC:2.7.11.30]
7048  
TGFBR2; transforming growth factor, beta receptor II (70/80kDa) [KO:K04388] [EC:2.7.11.30]
92  
ACVR2A; activin A receptor, type IIA [KO:K04670] [EC:2.7.11.30]
93  
ACVR2B; activin A receptor, type IIB [KO:K13596] [EC:2.7.11.30]
657  
BMPR1A; bone morphogenetic protein receptor, type IA [KO:K04673] [EC:2.7.11.30]
658  
BMPR1B; bone morphogenetic protein receptor, type IB [KO:K13578] [EC:2.7.11.30]
90  
ACVR1; activin A receptor, type I [KO:K04675] [EC:2.7.11.30]
7046  
TGFBR1; transforming growth factor, beta receptor 1 [KO:K04674] [EC:2.7.11.30]
91  
ACVR1B; activin A receptor, type IB [KO:K13567] [EC:2.7.11.30]
25805  
BAMBI; BMP and activin membrane-bound inhibitor [KO:K10162]
4086  
SMAD1; SMAD family member 1 [KO:K04676]
4090  
SMAD5; SMAD family member 5 [KO:K16790]
4093  
SMAD9; SMAD family member 9 [KO:K16791]
4087  
SMAD2; SMAD family member 2 [KO:K04500]
4088  
SMAD3; SMAD family member 3 [KO:K04500]
4089  
SMAD4; SMAD family member 4 [KO:K04501]
4091  
SMAD6; SMAD family member 6 [KO:K04677]
4092  
SMAD7; SMAD family member 7 [KO:K04677]
57154  
SMURF1; SMAD specific E3 ubiquitin protein ligase 1 [KO:K04678] [EC:6.3.2.19]
64750  
SMURF2; SMAD specific E3 ubiquitin protein ligase 2 [KO:K04678] [EC:6.3.2.19]
9372  
ZFYVE9; zinc finger, FYVE domain containing 9 [KO:K04679]
9765  
ZFYVE16; zinc finger, FYVE domain containing 16 [KO:K04679]
3397  
ID1; inhibitor of DNA binding 1, dominant negative helix-loop-helix protein [KO:K04680]
3398  
ID2; inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [KO:K17693]
3399  
ID3; inhibitor of DNA binding 3, dominant negative helix-loop-helix protein [KO:K17694]
3400  
ID4; inhibitor of DNA binding 4, dominant negative helix-loop-helix protein [KO:K17695]
5933  
RBL1; retinoblastoma-like 1 (p107) [KO:K04681]
1874  
E2F4; E2F transcription factor 4, p107/p130-binding [KO:K04682]
1875  
E2F5; E2F transcription factor 5, p130-binding [KO:K04682]
7027  
TFDP1; transcription factor Dp-1 [KO:K04683]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6667  
SP1; Sp1 transcription factor [KO:K04684]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
1030  
CDKN2B; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
5308  
PITX2; paired-like homeodomain 2 [KO:K04686]
9978  
RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
8454  
CUL1; cullin 1 [KO:K03347]
6500  
SKP1; S-phase kinase-associated protein 1 [KO:K03094]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
3458  
IFNG; interferon, gamma [KO:K04687]
7124  
TNF; tumor necrosis factor [KO:K03156]
387  
RHOA; ras homolog family member A [KO:K04513]
6093  
ROCK1; Rho-associated, coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
5519  
PPP2R1B; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
5518  
PPP2R1A; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
5515  
PPP2CA; protein phosphatase 2, catalytic subunit, alpha isozyme [KO:K04382] [EC:3.1.3.16]
5516  
PPP2CB; protein phosphatase 2, catalytic subunit, beta isozyme [KO:K04382] [EC:3.1.3.16]
6198  
RPS6KB1; ribosomal protein S6 kinase, 70kDa, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
6199  
RPS6KB2; ribosomal protein S6 kinase, 70kDa, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
130399  
ACVR1C; activin A receptor, type IC [KO:K13568] [EC:2.7.11.30]
4052  
LTBP1; latent transforming growth factor beta binding protein 1 [KO:K08023]
Reference
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
Reference
  Authors
Derynck R, Zhang YE.
  Title
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
  Journal
Nature 425:577-84 (2003)
Reference
  Authors
Massague J.
  Title
How cells read TGF-beta signals.
  Journal
Nat Rev Mol Cell Biol 1:169-78 (2000)
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)
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)
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)
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)
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)
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)
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)
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)
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)
KO pathway
 

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