INTERPLAY OF SIGNAL MEDIATORS OF DECAPENTAPLEGIC (DPP) - MOLECULAR CHARACTERIZATION OF MOTHERS AGAINST DPP, MEDEA, AND DAUGHTERS AGAINST DPP

Decapentaplegic (Dpp) plays an essential role in Drosophila developmen t, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracell ular signaling of the TGF-beta superfamily is mediated by Smad protein s, which are now grouped into three classes. Two Smads have been ident ified in Drosophila. Mothers against dpp (Mad) is a pathway-specific S mad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetic ally shown to antagonize Dpp signaling. Here we report the identificat ion of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor f or Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induce d Mad phosphorylation. Dad also blocks hetero-oligomerization and nucl ear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of M ad, and Dad inhibits this step Finally, we propose a model for Dpp sig naling by Drosophila Smad proteins.