Inositol polyphosphate multikinase in a nuclear PI3-kinase with transcriptional regulatory activity

Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) is a major intracellular messenger molecule thought to be formed almost exclusively by cytosolic, wortmannin-inhibited phosphoinositide 3-kinase (PI3K) family members. Inositol polyphosphate multikinase (IPMK), a member of a novel inositol polyphoaspate kinase family, was identified as an enzyme that generates a series of water-soluble inositol phosphates. The work outlined in this thesis describes the characterization of the robust, physiologic PI3K activity of IPMK, which is localized to nuclei and is unaffected by wortmannin. This activity is evolutionarily conserved and in yeast appears to physiologically regulate transcription and rapamycin sensitivity.