Fig. 2.

Detailed representation of TGF receptor–mediated signaling pathways and their regulatory mechanisms. This figure provides a thorough visual exploration of the complex interactions and activities instigated by the binding of TGF ligands to their type II and type III receptors (TGF-RII and TGF-RIII). It illustrates the consequential recruitment and phosphorylation of the type I receptor (TGF-RI), a pivotal action that triggers multiple signaling pathways. This intricate signaling network, including pathways controlled by SMAD2/SMAD3, Ras, and PI3K, is detailed in the figure, emphasizing their crucial role in activating specific transcription factors. The figure elaborates on the cascade effect that ensues, leading to the expression of genes that encode transcription factors instrumental in initiating epithelial to epithelial-to-mesenchymal transition (EMT). Furthermore, the figure delineates the activation of Akt by SMAD-independent pathways, such as PI3K and ILK. Akt’s subsequent limitation of GSK-3β activity is visually explained. This limitation is significant as GSK-3β is a kinase that inhibits the nuclear translocation of Snail and β-catenin, critical components in cellular transformation and movement. Moreover, Fig. 3 highlights the role of Smurf2 and SMAD6/SMAD7 in inhibiting SMAD signaling. It explains Smurf2’s function in degrading the active complex SMAD2/SMAD3/SMAD4 and SMAD6/SMAD7’s blockage of SMAD2/SMAD3 binding and phosphorylation at TGF-Rs