TGFB / Smad signaling (WP5382)

Homo sapiens

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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.

Authors

Andrea Arias Sáez , Diana Brancadoro , Denise Slenter , Egon Willighagen , Daniela Digles , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

trabecular meshwork cell

Pathway Ontology

transforming growth factor-beta Smad dependent signaling pathway

Participants
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Label Type Compact URI Comment
Smad3 GeneProduct uniprot:P84022
Smad2 GeneProduct uniprot:Q15796
SERPINE1 GeneProduct uniprot:P05121
Smad4 GeneProduct uniprot:Q13485
SPARC GeneProduct uniprot:P09486
CNN2 GeneProduct uniprot:P29279
POSTN GeneProduct uniprot:Q15063
PAI-1 Protein uniprot:P05121
TAZ Protein uniprot:Q9GZV5
TGFβ-I-R Protein uniprot:P36897
CTFG Protein uniprot:P29279
Sparc Protein uniprot:P09486
14-3-3 Protein uniprot:P61981
Periostin Protein uniprot:Q15063
TGFβ-II-R Protein uniprot:P37173
TGF-β Protein uniprot:P01137
ECM proteins Protein wikidata:Q193825
TGFβ-III-R Protein uniprot:Q03167 TGFβ type III receptor has exclusively a supporting role.

References

  1. Matrix control of transforming growth factor-β function. Horiguchi M, Ota M, Rifkin DB. J Biochem. 2012 Oct;152(4):321–9. PubMed Europe PMC Scholia
  2. The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. Wordinger RJ, Sharma T, Clark AF. J Ocul Pharmacol Ther. 2014;30(2–3):154–62. PubMed Europe PMC Scholia
  3. The role of matricellular proteins in glaucoma. Wallace DM, Murphy-Ullrich JE, Downs JC, O’Brien CJ. Matrix Biol. 2014 Jul;37:174–82. PubMed Europe PMC Scholia
  4. Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis. Walton KL, Johnson KE, Harrison CA. Front Pharmacol. 2017 Jul 14;8:461. PubMed Europe PMC Scholia
  5. Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review). Wang X, Huai G, Wang H, Liu Y, Qi P, Shi W, et al. Int J Mol Med. 2018 Mar;41(3):1201–12. PubMed Europe PMC Scholia
  6. TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs. Wilson SE. Exp Eye Res. 2021 Jun;207:108594. PubMed Europe PMC Scholia
  7. Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells. Li H, Raghunathan V, Stamer WD, Ganapathy PS, Herberg S. Front Cell Dev Biol. 2022 Mar 1;10:844342. PubMed Europe PMC Scholia
  8. TGF-β Superfamily Signaling in the Eye: Implications for Ocular Pathologies. Hachana S, Larrivée B. Cells. 2022 Jul 29;11(15):2336. PubMed Europe PMC Scholia