Mechanisms in TGF-β Action

Abstract
The various isoforms of TGF-β are multifunctional. We are exploring pathways of cellular regulation by TGF-β that lead to suppression of cell proliferation, modulation of cell adhesion and control of cell differentiation. These cellular responses appear to be activated by binding of TGF-β to a similar set of receptor glycoproteins in all cell types. TGF-β receptor types I and II are specifically lost in cell mutants that are resistant to TGF-β. The concomitant loss of these two receptors in certain mutants suggests that they are components of the TGF-β signal-transducing receptor complex. Inhibition of epithelial cell proliferation by TGF-β is linked to retention of the retinoblastoma growth suppressor gene product in an underphosphorylated state that is presumed to have growth suppressive activity. Inhibition of myogenic differentiation by TGF-β involves a block in the expression of the master myogenic differentiation genes, such as myogenin, but appears also to involve up-regulation of extracellular matrix production. Expression of components of the cell adhesion apparatus—cell adhesion receptors and extracellular matrix proteins—is controlled by TGF-β in an array of cell types. This response could have a great impact on the ability of cells to migrate, home to specific tissue locations and differentiate during development, invasion and metastasis.