Entry |
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Name |
TGF-beta signaling pathway
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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.
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Class |
Environmental Information Processing; Signal transduction
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Pathway map |

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Disease |
H00958 | Congenital stromal corneal dystrophy |
H01023 | Juvenile polyposis syndrome |
H01024 | Hereditary mixed polyposis syndrome |
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Other DBs |
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Reference |
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Authors |
Shi Y, Massague J. |
Title |
Mechanisms of TGF-beta signaling from cell membrane to the nucleus. |
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Reference |
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Authors |
Derynck R, Zhang YE. |
Title |
Smad-dependent and Smad-independent pathways in TGF-beta family signalling. |
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Reference |
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Authors |
Massague J. |
Title |
How cells read TGF-beta signals. |
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Reference |
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Authors |
Siegel PM, Massague J. |
Title |
Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. |
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Reference |
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Authors |
Shimasaki S, Moore RK, Otsuka F, Erickson GF. |
Title |
The bone morphogenetic protein system in mammalian reproduction. |
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Reference |
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Authors |
De Robertis EM, Larrain J, Oelgeschlager M, Wessely O. |
Title |
The establishment of Spemann's organizer and patterning of the vertebrate embryo. |
Journal |
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Reference |
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Authors |
Gumienny TL, Padgett RW. |
Title |
The other side of TGF-beta superfamily signal regulation: thinking outside the cell. |
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Reference |
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Authors |
Hamada H, Meno C, Watanabe D, Saijoh Y. |
Title |
Establishment of vertebrate left-right asymmetry. |
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Reference |
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Authors |
Chang H, Brown CW, Matzuk MM. |
Title |
Genetic analysis of the mammalian transforming growth factor-beta superfamily. |
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Reference |
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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 |
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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 |
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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. |
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Reference |
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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. |
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Reference |
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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. |
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Reference |
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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. |
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Reference |
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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. |
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Reference |
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Authors |
Anderson GJ, Frazer DM |
Title |
Iron metabolism meets signal transduction. |
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Reference |
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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. |
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Reference |
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Authors |
Ganz T, Nemeth E |
Title |
Iron homeostasis in host defence and inflammation. |
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Reference |
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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. |
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Reference |
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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. |
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Related pathway |
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KO pathway |
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