Sequential activation of ETS proteins provides a sustained transcriptional response to EGFR signaling

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Abstract

How signal transduction, which is dynamic and fluctuating by nature, is converted into a stable trancriptional response, is an unanswered question in developmental biology. Two ETS-domain transcription factors encoded by the pointed (pnt) locus, PntP1 and PntP2, are universal downstream mediators of EGFR-based signaling in Drosophila. Full disruption of pnt function in developing eye imaginal discs reveals a photoreceptor recruitment phenotype, in which only the R8 photoreceptor cell type is specified within ommatidia. Specific disruption of either pntP1 or pntP2 resulted in the same R8-only phenotype, demonstrating that both Pnt isoforms are essential for photoreceptor recruitment. We show that the two Pnt protein forms are activated in a sequential manner within the EGFR signaling pathway: MAPK phosphorylates and activates PntP2, which in turn induces pntP1 transcription. Once expressed, PntP1 is constitutively active and sufficient to induce target genes essential for photoreceptor development. Pulse-chase experiments indicate that PntP1 is stable for several hours in the eye disc. Sequential ETS-protein recruitment therefore allows sustained induction of target genes, beyond the transient activation of EGFR. © 2013.

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Shwartz, A., Yogev, S., Schejter, E. D., & Shilo, B. Z. (2013). Sequential activation of ETS proteins provides a sustained transcriptional response to EGFR signaling. Development (Cambridge), 140(13), 2746–2754. https://doi.org/10.1242/dev.093138

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