Eye transformer is a negative regulator of Drosophila JAK/STAT signaling.

signaling pathway is evolutionarily conserved and tightly regulated. We carried out a reporter-based genome-wide in vitro screen to identify genes that regulate Drosophila JAK/duanyu1813 pathway and found 5 novel regulators. Of these, CG14225 is a negative regulator structurally related to the Drosophila JAK/duanyu1813 pathway receptor Domeless, especially in the extracellular domain, and to the mammalian IL-6 receptor and the signal transducer gp130. CG14225 coimmunoprecipitates with Domeless and its associated kinase hopscotch in S2 cells. CG14225 duanyu1615 caused hyperphosphorylation of the transcription factor Stat92E in S2 cells on stimulation with the Drosophila JAK/duanyu1813 pathway ligand unpaired. CG14225 duanyu1615 in vivo hyperactivated JAK/duanyu1813 target genes on septic injury and enhanced unpaired-induced eye overgrowth, and was thus named the eye transformer (ET). In the gastrointestinal infection model, where JAK/duanyu1813 signaling is important for stem cell renewal, CG14225/ET duanyu1615 was protective in vivo. In conclusion, we have identified ET as a novel negative regulator of the Drosophila JAK/duanyu1813 pathway both in vitro and in vivo, and it functions in regulating Stat92E phosphorylation.

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