TGF-β: An Important Mediator of Allergic Disease and a Molecule with Dual Activity in Cancer Development

Figure 1

Synthesis and activation of TGF-β. TGF-β is synthesized as an inactive precursor with a preregion (signal peptide) and a proregion (N-terminal peptide LAP). Processing of the inactive form begins with the proteolytic cleavage of the signal peptide from pre-pro-TGF-β. After dimerization, TGF-β is cleaved by proteases (such as furin) at the C-terminal region in mature peptides and at the N-terminal LAP (latency-associated peptide). LAP-bound TGF-β forms small latent complexes (SLCs) that are transported to the extracellular matrix (ECM) where they can covalently bind to the binding protein (LTBP) to form a large latent complex released from the ECM by proteases. Then, the mature protein is cleaved from the LTBP in acidic conditions in vitro or by thrombospondin (TSP) or plasmin in vivo. Once the active TGF-β family member is released from the ECM, it can engage in signaling.