Multiple RTK pathways downregulate Groucho-mediated repression in Drosophila embryogenesis.
2008
RTK pathways establish cell fates in a wide range of developmental
processes. However, how the pathway effector MAPK coordinately regulates the
expression of multiple target genes is not fully understood. We have
previously shown that the EGFR RTK pathway causes phosphorylation and
downregulation of Groucho, a global co-repressor that is widely used by many
developmentally important repressors for silencing their various targets.
Here, we use specific antibodies that reveal the dynamics of Groucho
phosphorylation by MAPK, and show that Groucho is phosphorylated in response
to several RTK pathways during Drosophila embryogenesis. Focusing on
the regulation of terminal patterning by the Torso RTK pathway, we demonstrate
that attenuation of Groucho9s repressor function via phosphorylation is
essential for the transcriptional output of the pathway and for terminal cell
specification. Importantly, Groucho is phosphorylated by an efficient
mechanism that does not alter its subcellular localisation or decrease its
stability; rather, modified Groucho endures long after MAPK activation has
terminated. We propose that phosphorylation of Groucho provides a widespread,
long-term mechanism by which RTK signals control target gene expression.
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