Investigating if the linker phosphorylation sites in Drosophila Smad2 control its stability and transcriptional activity
Authors: Edward Eivers; Pablo Flota; Kenny Castro
Affiliation: California State University Los Angeles
Keywords: g. wing disc; g. wing disc
Signals from the transforming growth factor beta (TGF-β) superfamily of ligands has been shown to be important for cell fate determination, proliferation and differentiation during embryonic development and tissue homeostasis in the adult. This broad family of signaling molecules is typically divided into the bone morphogenetic protein (BMP) and Activin/TGF-β sub-families. Our labs interest, focuses on the activities of a group of TGF- β proteins known as receptor Smads (R-Smads). These transcription factors transmit intracellular signals for each pathway when phosphorylated in their C-terminal domains by ligand-activated transmembrane receptors. In this study, we identified four potential phosphorylation sites in the central linker domain of Drosophila Smad2 (dSmad2). We present data showing that mutation of these linker sites into non-phosphorylatable alanines resulted in stabilization of C-terminally phosphorylated dSmad2 proteins. We also found that when dSmad2 linker mutants were misexpressed in Drosophila wing imaginal discs using Gal4 drivers, adult wings were, reduced in size, bifurcated and displayed severely disrupted venation when compared to control wings. We are also investigating if mutation of the linker phosphorylation sites in dSmad2 can affect expression of downstream TGF- β target genes. In conclusion, our experiments aim to broaden our understanding of the signaling activities of the TGF-β pathway, in particular dSmad2 signal regulation and duration during Drosophila wing development.