In Drosophila, when Hh binds to its receptor Ptc, Ptc releases its inhibition of Smo, resulting in Smo's phosphorylation and stabilization at the plasma membrane. Smo then transmits a signal to a multi-protein complex that contains the kinase Fu, the kinesin-like Cos2 and the Gli-like transcription factor Ci. In their investigation of Cos2's role in Hh signalling in Drosophila on , Pascal Thérond's lab report that the phosphorylation of Cos2 by Fu induces it to undergo a conformational change that leads to this complex's disassembly, probably to free Ci to translocate to the nucleus to activate target genes. Their findings show that the Cos2 residue Ser572 is necessary for Hh signal transduction and is phosphorylated by Fu, either directly or indirectly. By using an antibody that specifically recognizes phosphorylated Ser572, the authors show that upon its phosphorylation, Cos2's association with Smo and Ci strongly decreases in vivo and in vitro. This study's results provide new mechanistic insights into Hh signal transduction,about which much remains unknown.
