Nuclear targeting of the beta isoform of Type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix7

Type II phosphatidylinositol phosphate kinases (PIPkins) have recently been found to be primarily phosphatidylinositol 5-phosphate 4-kinases, and thei r physiological role remains unclear. We have previously shown that a Type II PIPkin [isoform(s) unknown], is localized partly in the nucleus [Divecha , Rhee, Letcher and Irvine(1993) Biochem. J. 289, 617-620], and here we sho w, by transfection of HeLa cells with green-fluorescent-protein-tagged Type II PIPkins, that this is likely to be the Type II beta isoform. Type II be ta PIPkin has no obvious nuclear localization sequence, and a detailed anal ysis of the localization of chimaeras and mutants of the alpha (cytosolic) and beta PIPkins shows that the nuclear localization requires the presence of a 17-amino-acid length of alpha-helix (alpha-helix 7) that is specific t o. the beta isoform, and that this helix must be present in its entirety, w ith a precise orientation. This resembles the nuclear targeting of the HIV protein Vpr, and Type II beta PIPkin is apparently therefore the first exam ple of a eukaryotic protein that uses the same mechanism.