KEGG PATHWAY: hsa04350

PATHWAY: hsa04350

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

Pathway map

hsa04350

TGF-beta signaling pathway

Disease

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)

Other DBs

BSID:

83064

GO:

0007179

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 homolog (Xenopus laevis) [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:K04680]
3399	ID3; inhibitor of DNA binding 3, dominant negative helix-loop-helix protein [KO:K04680]
3400	ID4; inhibitor of DNA binding 4, dominant negative helix-loop-helix protein [KO:K04680]
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 myelocytomatosis viral oncogene homolog (avian) [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]
9475	ROCK2; Rho-associated, coiled-coil containing protein kinase 2 [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

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)

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)

Reference

PMID:11252892

Authors

Massague J.

Title

How cells read TGF-beta signals.

Journal

Nat Rev Mol Cell Biol 1:169-78 (2000)

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)

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)

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)

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)

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)

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)

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)

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)

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)

KO pathway

ko04350

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (1)   
   BioSystems (1)   
Disease (25)   
   KEGG DISEASE (25)   
Drug (13)   
   KEGG DRUG (13)   
Genome (1)   
   KEGG GENOME (1)   
Gene (81)   
   KEGG GENES (81)   
All databases (122)   

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