TGFB / Smad signaling (Homo sapiens)

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2, 4-8337nucleusextracellular spaceECM degradationcytoplasmTGF-β response genesSERPINE114-3-3TAZPOSTNSPARCCTFGSparcSmad2Smad3PeriostinPAI-1Smad4CNN2TGFβ-I-RPTGFβ-II-RSmad2Smad3PPSmad2Smad3PPSmad4TAZSmad2PSmad3PSmad4Under pathological conditions, ECM proteins accumulates in the extracelullar space leading to an increase in the aqueous humor outflow resistance and ocular hypertension.1, 8TGF-βECM proteinsECM proteins744TGFβ-III-RTAZP14-3-3TAZPCell adhesionProliferationMigrationTAZSmad2PSmad3PSmad4ECM proteins


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.

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Ontology Terms

 

Bibliography

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  1. Hachana S, Larrivée B; ''TGF-β Superfamily Signaling in the Eye: Implications for Ocular Pathologies.''; Cells, 2022 PubMed Europe PMC Scholia
  2. Horiguchi M, Ota M, Rifkin DB; ''Matrix control of transforming growth factor-β function.''; J Biochem, 2012 PubMed Europe PMC Scholia
  3. 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
  4. 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
  5. 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
  6. 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
  7. Walton KL, Johnson KE, Harrison CA; ''Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis.''; Front Pharmacol, 2017 PubMed Europe PMC Scholia
  8. 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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CompareRevisionActionTimeUserComment
129730view01:43, 22 May 2024EweitzOntology Term : 'trabecular meshwork cell' added !
129729view01:43, 22 May 2024EweitzModified title
126867view11:31, 28 June 2023Ddiglescorrected UniProt accession numbers
126821view10:39, 25 June 2023EgonwIdentifier is from Wikidata
126817view10:22, 24 June 2023Andreaarias99
126816view10:07, 24 June 2023DianabrancadoroModified description
126812view09:44, 23 June 2023Andreaarias99Regulation 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 f
126807view17:01, 22 June 2023Andreaarias99
126790view13:58, 22 June 2023DeSlOntology Term : 'transforming growth factor-beta Smad dependent signaling pathway' added !
126753view14:35, 18 June 2023Andreaarias99
126725view14:42, 15 June 2023Dianabrancadoro
126723view14:41, 15 June 2023Dianabrancadoro
126720view13:53, 15 June 2023Dianabrancadoro
126719view13:49, 15 June 2023Dianabrancadoro
126713view14:52, 14 June 2023Dianabrancadoro
126691view12:32, 13 June 2023Andreaarias99New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
14-3-3ProteinP61981 (Uniprot-TrEMBL)
CNN2GeneProductP29279 (Uniprot-TrEMBL)
CTFGProteinP29279 (Uniprot-TrEMBL)
ECM proteinsProteinQ193825 (Other)
PAI-1ProteinP05121 (Uniprot-TrEMBL)
POSTNGeneProductQ15063 (Uniprot-TrEMBL)
PeriostinProteinQ15063 (Uniprot-TrEMBL)
SERPINE1GeneProductP05121 S (Uniprot-TrEMBL)
SPARCGeneProductP09486 (Uniprot-TrEMBL)
Smad2GeneProductQ15796 (Uniprot-TrEMBL)
Smad3GeneProductP84022 (Uniprot-TrEMBL)
Smad4GeneProductQ13485 (Uniprot-TrEMBL)
SparcProteinP09486 (Uniprot-TrEMBL)
TAZProteinQ9GZV5 (Uniprot-TrEMBL)
TGF-βProteinP01137 (Uniprot-TrEMBL)
TGFβ-I-RProteinP36897 (Uniprot-TrEMBL)
TGFβ-II-RProteinA3QNQ0 (Uniprot-TrEMBL)
TGFβ-III-RProteinQ03167 (Uniprot-TrEMBL) TGFβ type III receptor has exclusively a supporting role.

Annotated Interactions

No annotated interactions

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