Figure 8.

Model of the Dpp signaling pathway: cascades of phosphorylation and dynamic rearrangement of protein interactions. Dpp induces hetero-oligomerization of Punt and Tkv. Punt activates Tkv by transphosphorylating the juxtamembrane region. Activated Tkv phosphorylates Mad. Mad forms homo-oligomeric complexes and/or hetero-oligomeric complexes with Medea. It is not known whether Mad homo-oligomers have specific activity in vivo. Hetero-oligomers of Mad and Medea translocate into the nucleus where they transactivate target genes such as vestigial. Dad is one such target, and its expression is induced by Dpp. Dad stably binds to Tkv and interrupts phosphorylation of Mad by Tkv. The numbers of each Smad molecule in the homo- and hetero-oligomeric complexes remain to be determined.