TGFβ/Smad signaling pathway (Homo sapiens)
From WikiPathways
Description
Regulation of TGFβ/Smad Signaling Pathway in Trabecular Meshwork (TM) cells. In this pathway, TGF-β binds to the TGF-β-type II receptor, inducing the activation of the TGF-β-type-I receptor. This induces the phosphorylation of Smad2/3 proteins which form a complex with Smad4. The translocation of this complex to the nucleus is facilitated by the TAZ protein. Once in the nucleous, it binds to SBEs (Smad Binding Elements), promoting the transcription of TGF-beta-response genes. The inhibition of this translocation instead occurs when phosphorylated TAZ protein interacts with 14-3-3 protein preventing the formation of complex TAZ-Smad.
The translated ECM proteins are secreted by TM cells to the extracellular space.
This pathway is based on Figure 4 of the publication “Mutual regulation of the Hippo/Wnt/LPA/TGF-β signaling pathways and their roles in glaucoma (Review)” by Xin Wang, Guoli Huai, Hailian Wang, Yuande Liu, Ping Qi, Wei Shi, Jie Peng, Hongji Yang, Shaoping Deng, and Yi Wang.Quality Tags
Ontology Terms
Saving...Bibliography
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- Hachana S, Larrivée B; ''TGF-β Superfamily Signaling in the Eye: Implications for Ocular Pathologies.''; Cells, 2022 PubMed Europe PMC Scholia
- Horiguchi M, Ota M, Rifkin DB; ''Matrix control of transforming growth factor-β function.''; J Biochem, 2012 PubMed Europe PMC Scholia
- Wordinger RJ, Sharma T, Clark AF; ''The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma.''; J Ocul Pharmacol Ther, 2014 PubMed Europe PMC Scholia
- Li H, Raghunathan V, Stamer WD, Ganapathy PS, Herberg S; ''Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells.''; Front Cell Dev Biol, 2022 PubMed Europe PMC Scholia
- Wang X, Huai G, Wang H, Liu Y, Qi P, Shi W, Peng J, Yang H, Deng S, Wang Y; ''Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review).''; Int J Mol Med, 2018 PubMed Europe PMC Scholia
- Wilson SE; ''TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs.''; Exp Eye Res, 2021 PubMed Europe PMC Scholia
- Walton KL, Johnson KE, Harrison CA; ''Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis.''; Front Pharmacol, 2017 PubMed Europe PMC Scholia
- Wallace DM, Murphy-Ullrich JE, Downs JC, O'Brien CJ; ''The role of matricellular proteins in glaucoma.''; Matrix Biol, 2014 PubMed Europe PMC Scholia
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| 14-3-3 | Protein | P61981 (Uniprot-TrEMBL)  | |
| CNN2 | GeneProduct | P29279 (Uniprot-TrEMBL) | |
| CTFG | Protein | P29279 (Uniprot-TrEMBL) | |
| ECM proteins | Protein | Q193825 (Wikidata) | |
| PAI-1 | Protein | P05121 (Uniprot-TrEMBL) | |
| POSTN | GeneProduct | Q15063 (Uniprot-TrEMBL) | |
| Periostin | Protein | Q15063 (Uniprot-TrEMBL) | |
| SERPINE1 | GeneProduct | P05121 (Uniprot-TrEMBL) | |
| SPARC | GeneProduct | P09486 (Uniprot-TrEMBL) | |
| Smad2 | GeneProduct | Q15796 (Uniprot-TrEMBL) | |
| Smad3 | GeneProduct | P84022 (Uniprot-TrEMBL) | |
| Smad4 | GeneProduct | Q13485 (Uniprot-TrEMBL) | |
| Sparc | Protein | P09486 (Uniprot-TrEMBL) | |
| TAZ | Protein | Q9GZV5 (Uniprot-TrEMBL) | |
| TGF-β | Protein | P01137 (Uniprot-TrEMBL) | |
| TGFβ-I-R | Protein | P36897 (Uniprot-TrEMBL) | |
| TGFβ-II-R | Protein | P37173 (Uniprot-TrEMBL) | |
| TGFβ-III-R | Protein | Q03167 (Uniprot-TrEMBL) | TGFβ type III receptor has exclusively a supporting role. |
Annotated Interactions
No annotated interactions
