Genetics, Vol. 154, 695-712, February 2000, Copyright © 2000

A Genetic Screen for Novel Components of the Ras/Mitogen-Activated Protein Kinase Signaling Pathway That Interact With the yan Gene of Drosophila Identifies split ends, a New RNA Recognition Motif-Containing Protein

Ilaria Rebaya,c, Fangli Chena, Francis Hsiaoa, Peter A. Kolodziejb, Bing H. Kuangb, Todd Lavertyc, Chris Suhc, Matthew Voasa, Andrina Williamsa, and Gerald M. Rubinc
a Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142,
b Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0295
c Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720

Corresponding author: Ilaria Rebay, Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142., rebay{at}wi.mit.edu (E-mail)

Communicating editor: R. S. HAWLEY

The receptor tyrosine kinase (RTK) signaling pathway is used reiteratively during the development of all multicellular organisms. While the core RTK/Ras/MAPK signaling cassette has been studied extensively, little is known about the nature of the downstream targets of the pathway or how these effectors regulate the specificity of cellular responses. Drosophila yan is one of a few downstream components identified to date, functioning as an antagonist of the RTK/Ras/MAPK pathway. Previously, we have shown that ectopic expression of a constitutively active protein (yanACT) inhibits the differentiation of multiple cell types. In an effort to identify new genes functioning downstream in the Ras/MAPK/yan pathway, we have performed a genetic screen to isolate dominant modifiers of the rough eye phenotype associated with eye-specific expression of yanACT. Approximately 190,000 mutagenized flies were screened, and 260 enhancers and 90 suppressors were obtained. Among the previously known genes we recovered are four RTK pathway components, rolled (MAPK), son-of-sevenless, Star, and pointed, and two genes, eyes absent and string, that have not been implicated previously in RTK signaling events. We also isolated mutations in five previously uncharacterized genes, one of which, split ends, we have characterized molecularly and have shown to encode a member of the RRM family of RNA-binding proteins.




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