Figure 1.

Mature TGF-β ligand, LAP, and LTBP together form a large latency complex that keeps the TGF-β ligand in a latent state at this time. When the TGF-β ligand is released from the complex, it changes from a latent to an active state. The released TGF-β ligand can directly bind to TβR II, thereby further binding to TβR I, but TGF-β ligand cannot directly bind to TβR I. The combination of TGF-β ligand, TβR II, and TβR I can further transmit signals to downstream mediators. After phosphorylation and activation of SMAD2 and SMAD3, they further bind to SMAD4 and transmit the signal to the nucleus.