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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: Cytokine Growth Factor Rev. 2020 Oct 6;57:39–54. doi: 10.1016/j.cytogfr.2020.09.003

Figure 1. The TGF-β signaling pathway.

Figure 1.

A. Schematic representation of TGF-β family pathway activation and action. Dimeric ligand binding induces assembly of two type I- and two type II-receptors into a hexameric signaling complex, allowing the type II receptors to activate the type I receptors by phosphorylation. The active type I receptors in turn phosphorylate R-SMADs, which then form trimeric complexes with SMAD4, translocate to the nucleus and regulate gene expression. R-SMADs are divided in two functionally different branches, the SMAD1/5/8 branch (a.k.a. “the BMP-pathway”), and the SMAD2/3 branch (a.k.a. “the Activin/TGF-β-pathway”). Ligands on the left side are colored blue, on the right side they are colored green to represent their pathway selectivity. Downstream gene regulation, therefore, depends on which type I receptor forms part of the active signaling complexes. B. The TGF-β/activin and the BMP subfamilies each share a subset of type I receptors and downstream effector SMADs. Notably, the family has over 33 ligand genes in humans but only five type II and seven type I receptors, indicating that there is substantial overlap in receptor utilization.