Signaling by transforming growth factor-(β superfamily members is initiated when ligand binds to and induces formation of a heteromeric receptor complex composed of type I and type II serine/threonine kinase receptors (reviewed inrefs.1 –4 ). Upon formation of this complex, receptor II phosphorylates receptor I in a highly conserved juxtamembrane region, known as the GS domain. Phosphorylated receptor I is then activated to phosphorylate its downstream targets, the members of the Smad family of proteins. These Smads are now known to be the critical intracellular mediators of TGF-(β superfamily signaling (reviewed inrefs.1 –4 ).
