KEGG PATHWAY: map04350

PATHWAY: map04350

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

Environmental Information Processing; Signal transduction

Pathway map

map04350

TGF-beta signaling pathway

Other DBs

GO:

0007179

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

map04010

MAPK signaling pathway

map04110

Cell cycle

map04120

Ubiquitin mediated proteolysis

map04210

Apoptosis

KO pathway

ko04350

All links

Gene (150079)   
   MGENES (27719)   
   RefGene (122360)   
All databases (150079)   

Download RDF

DBGET integrated database retrieval system