Originally published as Genetics Published Articles Ahead of Print on February 2, 2009.

Genetics, Vol. 181, 1335-1345, April 2009, Copyright © 2009
doi:10.1534/genetics.108.098475

Identification of Receptor-Tyrosine-Kinase-Signaling Target Genes Reveals Receptor-Specific Activities and Pathway Branchpoints During Drosophila Development

John R. Leatherbarrow^* and Marc S. Halfon^*,,,,1

^* Department of Biochemistry and Department of Biology, State University of New York, Buffalo, New York 14214, New York State Center of Excellence in Bioinformatics and the Life Sciences, Buffalo, New York 14203 and Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263

¹ Corresponding author: State University of New York at Buffalo, 701 Ellicott St., Buffalo, NY 14203.
E-mail: mshalfon{at}buffalo.edu

Receptor tyrosine kinases (RTKs) are an important family of signaling molecules with the unusual property that they are able to transduce their signals using the same downstream pathways. This has led to an unresolved debate as to whether individual receptors are interchangeable, or if each receptor can mediate specific downstream responses. To address this question, we have conducted a screen to identify target genes whose expression is differentially modulated by RTKs and their downstream pathway components. Using whole-mount in situ hybridization in Drosophila embryos exposed to constitutively active RTK pathway signaling, along with quantitative RT–PCR, we found that a significant fraction of target genes respond differentially in a spatial and/or quantitative manner. This includes differential responses to EGF receptor vs. fibroblast growth factor receptor signaling as well as to more downstream components such as Ras1 and pointed. We show that not only genes but also individual alternative transcripts can respond differently to signaling, and we present evidence that the differential responses can be mediated at the transcriptional level. Our results demonstrate that different RTKs can elicit distinct transcriptional responses, and the target genes obtained from our screen provide a valuable resource for further exploration of the mechanisms underlying this signaling specificity.

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Genetics 2009 181: NP. [Full Text]  

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Online ISSN: 1943-2361  Print ISSN: 0016-6731
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