TY - JOUR T1 - Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. JF - Genes Dev Y1 - 2005 A1 - Baeg, Gyeong-Hun A1 - Zhou, Rui A1 - Perrimon, Norbert KW - Active Transport, Cell Nucleus KW - Animals KW - Cell Line KW - Cell Nucleus KW - DNA-Binding Proteins KW - Drosophila Proteins KW - Janus Kinase 1 KW - Phosphorylation KW - Protein Tyrosine Phosphatases KW - Protein Tyrosine Phosphatases, Non-Receptor KW - Protein-Tyrosine Kinases KW - Repressor Proteins KW - RNA Interference KW - Signal Transduction KW - STAT Transcription Factors KW - Suppressor of Cytokine Signaling Proteins KW - Trans-Activators KW - Tyrosine AB -

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.

VL - 19 IS - 16 U1 - http://www.ncbi.nlm.nih.gov/pubmed/16055650?dopt=Abstract ER -