The role of endocytic pathways in TGF-β signaling.

Transforming growth factor β (TGF-β) superfamily consists of numerous cytokins that regulate various cellular processes. TGF-β, the prototype of the family, signals through its cell surface serine/threonin kinase receptors and besides its role in cell differentiation, migration, adhesion etc. it is also able to induce epithelial-mesenchymal (EMT) transition via both Smad- pathway and MAPK- pathway. Among the different types of epithelial-mesenchymal transition, type II that is described to be associated with wound healing, tissue regeneration, organ fibrosis and is induced upon inflammatory stimuli. It can be triggered by secretion of growth factors such as TGF-β, EGF. Different endocytic routes are used for the internalization of TGF-β ligand and its receptors and these pathways can control the activity of downstream events. Internalization via clathrin-coated vesicles promotes the signaling while the caveola-mediated endocytosis plays important role in the termination of the events, although the steps of the latter event are less clear. The early endosome is considered a clue compartment in promoting the signaling. Recently published data suggest that the early endosome plays crucial role in the termination of the TGFβ signaling as well. It is not only maintain a special environment for the effective signaling but can direct the internalized cargos towards degradative pathways (multivesicular bodies, lysosomes).