Document Detail

Sequential activation of ETS proteins provides a sustained transcriptional response to EGFR signaling.
MedLine Citation:
PMID:  23757412     Owner:  NLM     Status:  In-Data-Review    
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.
Arkadi Shwartz; Shaul Yogev; Eyal D Schejter; Ben-Zion Shilo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  2746-54     Citation Subset:  IM    
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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