Identification of receptor-tyrosine-kinase-signaling target genes reveals receptor-specific activities and pathway branchpoints during Drosophila development.

Abstract:

: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.

journal_name

Genetics

journal_title

Genetics

authors

Leatherbarrow JR,Halfon MS

doi

10.1534/genetics.108.098475

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1335-45

issue

4

eissn

0016-6731

issn

1943-2631

pii

genetics.108.098475

journal_volume

181

pub_type

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