MECHANISM OF ACTIVATION OF THE TGF-BETA RECEPTOR

Transforming growth factor-beta (TGF-beta) signals by contacting two d istantly related transmembrane serine/threonine kinases called recepto rs I and II. The role of these molecules in signalling has now been de termined. TGF-beta binds directly to receptor II, which is a constitut ively active kinase. Bound TGF-beta is then recognized by receptor I w hich is recruited into the complex and becomes phosphorylated by recep tor II. Phosphorylation allows receptor I to propagate the signal to d ownstream substrates. This provides a mechanism by which a cytokine ca n generate the first step of a signalling cascade.