ERK signaling during terminal patterning of the Drosophila embryo

Abstract

The ERK signaling pathway is able to control a variety of cellular processes such as cell differentiation, growth, migration and apoptosis, and has been implicated in various human diseases, such as cancers and neurodegenerative diseases. It has traditionally been viewed as transferring information in a unidirectional manner. In this work, we look at how information is transferred in both directions, downstream and upstream the pathway, by studying ERK signaling during <bold>Drosophila</bold> embryogenesis

We first look at how ERK signaling controls gene expression via the relief of repression of the transcription factor Capicua. By making use of genetic, biochemical, imaging and modeling techniques we find that ERK signaling affects Capicua's nuclear shuttling abilities and reduces its stability, thereby reducing overall protein levels and allowing for the de-repression of target genes during terminal patterning of the <bold>Drosophila</bold> embryo.

The ERK signaling pathway is often viewed as a set of three independent phosphorylation-dephosphorylation modules in which information is transferred in a unidirectional manner. We challenge this idea by perturbing the level of expression of multiple pathway components, and find that activation of multiple kinases along the pathway can be retroactively controlled by their own substrates; specifically, we find that just like ERK substrates can control ERK activation, ERK itself can retroactively control MEK activation. Furthermore, we find that ERK substrates are also able to affect MEK activation via an unknown mechanism.