Regulating the stability of TGF beta receptors and Smads

Transforming growth factor beta (TGF beta) controls cellular behavior in embryonic and adult tissues. TGF beta binding to serine/threonine kinase receptors on the plasma membrane activates Smad molecules and additional signaling proteins that together regulate gene expression. In this review, mechanisms and models that aim at explaining the coordination between several components of the signaling network downstream of TGF beta are presented. We discuss how the activity and duration of TGF beta receptor/Smad signaling can be regulated by post-translational modifications that affect the stability of key proteins in the pathway. We highlight links between these mechanisms and human diseases, such as tissue fibrosis and cancer.