Regulating the stability of TGFbeta receptors and Smads.
Transforming growth factor beta (TGFbeta) controls cellular behavior in embryonic and adult tissues. TGFbeta 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 TGFbeta are presented. We discuss how the activity and duration of TGFbeta 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.
Lönn
Peter
P
Ludwig Institute for Cancer Research, Uppsala University, Box 595, Biomedical Center, SE-751 24 Uppsala, Sweden.
Morén
Anita
A
Raja
Erna
E
Dahl
Markus
M
Moustakas
Aristidis
A
D006801:Humans; D055550:Protein Stability; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051897:Smad Proteins, Inhibitory / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D051897:Smad Proteins, Inhibitory; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta