Investigating the transcriptional responses to RTK signaling
Signaling mediated by Receptor tyrosine kinases (RTK) often leads to changes in gene expression. Accordingly, nuclear factors that are directly phosphorylated by MAPK play key roles in interpreting signals relayed by RTK pathways. For many years it had been assumed that most RTK responses in Drosophila are mediated by nuclear effectors belong to the Ets transcription factor super-family, such as Pointed and Yan. More recently, however, it has emerged that additional transcriptional regulators are direct substrates of MAPK/Erk. In particular, the induction of many RTK targets involves the phosphorylation and down-regulation of the repressor proteins Groucho and Capicua. Furthermore, phosphorylation of Groucho also provides a mechanism of long-term derepression, allowing prolonged transcription of RTK targets after transient MAPK/Erk activity has declined. To better understand how RTK signaling is interpreted in stimulated cells, and how this information is integrated with other cellular inputs, we are in the process of uncovering novel nuclear MAPK/Erk substrates. We expect their identification to provide insights into the transcriptional regulation underlying the changes in cell fate specification elicited by RTK signaling during development.