Figure 1.

Signaling by ligands of the TGF-β superfamily in the thymus. Members of the TGF-β superfamily may signal by either the TGF-β (reddish) or the BMP branch (bluish). Upon binding to type II serine/threonine receptors occurs the recruitment of type I receptors, which further phosphorylate Smad proteins. Whereas ActRIIA and ActRIIB may be shared between both pathways, TβRII and BMPRII are specific to TGF-β and BMP signaling, respectively. In general, Smad2 and Smad3 relay signals from the Alk4, Alk5, and Alk7 receptors, while Smad1, Smad5, and Smad8/9 are phosphorylated by Alk2, Alk3, and Alk6 receptors. However, Alk2, Alk6, and Alk7 are not expressed during thymocyte maturation. Modulation of gene expression occurs after Smad complex translocates into the nucleus and depends on the interaction with additional protein complexes (not shown).