| The JAK-STAT pathway participates in a wide range of developmental events which when going awry can lead to serious conditions including cancer and immune disease. Taking advantage of the in vivo model system of Drosophila we attempt an initial functional characterization of two novel JAK-STAT pathway components.; One, called dPIAS whose mammalian homologue PIAS for Protein Inhibitor of Activated STAT, had first been identified in mammals where it was physically associated with activated STATs. It had been shown to be an inhibitor of STAT function when overexpressed in tissue culture as shown in luciferase reporter assays with artificial promoters.; The other, was found to be an isoform of dSTAT encoded by the single STAT locus known in Drosophila, stat92E. It was called ΔN-dSTAT and represents the first N-terminally truncated STAT.; In a series of genetic, biochemical and transgenic experiments we demonstrate that dPIAS is a negative regulator of dSTAT activity in vivo in a variety of developmental settings. For example, it is crucial for the regulation of activated dSTAT in viability/fertility, blood cell, wing and eye development. We also give genetic evidence that dSTAT is required for growth and determination of the eye. Furthermore we show that ΔN-dSTAT when overexpressed in vivo acts as a dominant negative STAT in eye development. |
