The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway
NaturePublished 1 August 1994
Damian Brunner, Klaus Dücker, Nadja Oellers, Ernst Hafen, Henrike Scholz, Christian Klämbt
Citations361
SJR quartileQ1
SJR score18.29
SNIP10.16
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TL;DR
Genetic and biochemical data are presented suggesting that MAP kinase controls neural development through phosphorylation of two antagonizing transcription factors of the ETS family, Van and PntP2.
Abstract
The fate of the R7 photoreceptor cell in the developing eye of Drosophila is controlled by the Sevenless (Sev) receptor tyrosine kinase. Sev activates a highly conserved signal transduction cascade involving the proteins Ras1 and Raf and the Rolled/mitogen-activated protein (Rl/MAP) kinase. Here we show that the ETS domain protein encoded by the P2 transcript of the pointed (pnt) gene is a nuclear target of this signalling cascade which acts downstream of Rl/MAP kinase. The PntP2 protein is phosphorylated by Rl/MAP kinase in vitro at a single site and this site is required for its function in vivo. Furthermore, we present genetic and biochemical data suggesting that MAP kinase controls neural development through phosphorylation of two antagonizing transcription factors of the ETS family, Yan and PntP2.
Keywords
Biochemistry, Genetics and Molecular Biology
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The EMBO JournalActivation of ternary complex factor Elk‐1 by MAP kinases.
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CellA gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways
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Genes & DevelopmentA group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo.
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