Eyes absent mediates cross-talk between retinal determination genes and the receptor tyrosine kinase signaling pathway.
Eyes absent (eya) encodes a member of a network of nuclear transcription factors that promotes eye development in both vertebrates and invertebrates. Despite extensive studies, the molecular mechanisms whereby cell-cell signaling pathways coordinate the function of this retinal determination gene network remain unknown. Here, we report that Drosophila Eya function is positively regulated by mitogen-activated protein kinase (MAPK)-mediated phosphorylation and that this regulation extends to developmental contexts independent of eye determination. In vivo genetic analyses, together with in vitro kinase assay results, demonstrate that Eya is a substrate for extracellular signal-regulated kinase, the MAPK acting downstream in the receptor tyrosine kinase (RTK) signaling pathway. Thus, phosphorylation of Eya appears to provide a direct regulatory link between the RTK/Ras/MAPK signaling cascade and the retinal determination gene network.
Hsiao
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FC
Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
Williams
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A
Davies
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EL
Rebay
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I
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020239:Receptor Cross-Talk / Q000502:physiology; D012160:Retina / Q000196:embryology*; D048051:p38 Mitogen-Activated Protein Kinases
D029721:Drosophila Proteins; D005136:Eye Proteins; C092694:eya protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C086795:rl protein, Drosophila; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases