PathWhiz

Pathway Description

TGF beta SMAD Signaling

Homo sapiens

Signaling Pathway

The TGF-β pathway is initiated when TGF-β activates TGF-β receptors (type-1/2) on the cell surface. This receptor activation leads to the phosphorylation of the receptors, which in turn activates downstream signaling components. One important result is the phosphorylation of Mothers against decapentaplegic homolog 2 (SMAD2), forming a complex called SMAD2 with phosphate. This phosphorylated SMAD2 then activates a critical downstream signaling cascade involving SMAD2-3-4, which translocates from the cytosol to the nucleus, where it regulates gene expression and various cellular responses. However, the pathway is also tightly regulated. SMAD 6/7 interacts with SMURF 1/2, which acts as a negative regulator by inhibiting the phosphorylation of the TGF-β receptor. This feedback mechanism helps to balance the activation of the TGF-β pathway to ensure proper cellular responses.

References

TGF beta SMAD Signaling References

Massagué, J., & Sheppard, D. (2023). TGF-β signaling in health and disease. Cell, 186(19), 4007-4037. https://doi.org/10.1016/j.cell.2023.07.036

Huang, F., Chen, YG. Regulation of TGF-β receptor activity. Cell Biosci 2, 9 (2012). https://doi.org/10.1186/2045-3701-2-9

Deng, Z., Fan, T., Xiao, C. et al. TGF-β signaling in health, disease and therapeutics. Sig Transduct Target Ther 9, 61 (2024). https://doi.org/10.1038/s41392-024-01764-w

Akhurst, R., Hata, A. Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov 11, 790–811 (2012). https://doi.org/10.1038/nrd3810

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Visualize Compound Data

Phosphate

Visualize Protein Data

		E3 ubiquitin ligase SMURF1
		E3 ubiquitin-protein ligase SMURF2
		Mothers against decapentaplegic homolog 2
		Mothers against decapentaplegic homolog 3
		Mothers against decapentaplegic homolog 4
		Mothers against decapentaplegic homolog 6
		Mothers against decapentaplegic homolog 7
		Pituitary homeobox 2
		TGF-beta receptor type-1
		TGF-beta receptor type-2
		Transforming growth factor beta-1
		Transforming growth factor beta-2
		Transforming growth factor beta-3