Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila
Abstract
The cytokine-activated Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays an important role in the control of a wide variety of biological processes. When misregulated, JAK/STAT signaling is associated with various human diseases, such as immune disorders and tumorigenesis. To gain insights into the mechanisms by which JAK/STAT signaling participates in these diverse biological responses, we carried out a genome-wide RNA interference (RNAi) screen in cultured Drosophila cells. We identified 121 genes whose double-stranded RNA (dsRNA)-mediated knockdowns affected STAT92E activity. Of the 29 positive regulators, 13 are required for the tyrosine phosphorylation of STAT92E. Furthermore, we found that the Drosophila homologs of RanBP3 and RanBP10 are negative regulators of JAK/STAT signaling through their control of nucleocytoplasmic transport of STAT92E. In addition, we identified a key negative regulator of Drosophila JAK/STAT signaling, protein tyrosine phosphatase PTP61F, and showed that it is a transcriptional target of JAK/STAT signaling, thus revealing a novel negative feedback loop. Our study has uncovered many uncharacterized genes required for different steps of the JAK/STAT signaling pathway.
Keywords
Footnotes
-
Supplemental material is available at http://genesdev.org.
-
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1320705.
-
Supplementary Table 1 lists the information on the dsRNAs. Please note that the results obtained with dsRNAs with potential off-target effects will need further validation with newly synthesized independent dsRNAs.
-
↵2 These authors contributed equally to this work.
-
↵3 Corresponding author.
↵3 E-MAIL perrimon{at}receptor.med.harvard.edu; FAX (617) 432-7688.
-
- Accepted June 20, 2005.
- Received April 1, 2005.
- Cold Spring Harbor Laboratory Press