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Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila
- Source :
- Genes & Development. 19:1861-1870
- Publication Year :
- 2005
- Publisher :
- Cold Spring Harbor Laboratory, 2005.
-
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.
- Subjects :
- Active Transport, Cell Nucleus
Suppressor of Cytokine Signaling Proteins
Biology
stat
Cell Line
chemistry.chemical_compound
Genetics
Animals
Drosophila Proteins
Protein inhibitor of activated STAT
SOCS3
Phosphorylation
STAT4
STAT6
Cell Nucleus
Tyrosine phosphorylation
Janus Kinase 1
Protein-Tyrosine Kinases
Protein Tyrosine Phosphatases, Non-Receptor
Research Papers
Cell biology
DNA-Binding Proteins
Repressor Proteins
STAT Transcription Factors
chemistry
Trans-Activators
STAT protein
Tyrosine
RNA Interference
Protein Tyrosine Phosphatases
Janus kinase
Signal Transduction
Developmental Biology
Subjects
Details
- ISSN :
- 15495477 and 08909369
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Genes & Development
- Accession number :
- edsair.doi.dedup.....563ebb3729bd791aa8c98b4bc25fa455