title: When worlds collide: inositol pyrophosphates and phosphoinositides intersect at the plasma membrane.
abstract: Highly phosphorylated inositol pyrophosphates are present in the cells of many organisms such as yeast, Dictyostelium and mammals. They can act as signal molecules in growth factor and insulin signalling both in cultured cells and in intact mice. Their action involves protein pyrophosphorylation or binding to multiple protein interactors such as PH (pleckstrin homology)-domain-containing proteins. One key enzyme in their synthesis, PPIP5K (diphosphoinositol pentakisphosphate kinase) 1/2, can phosphorylate InsP6 and 5-InsP7 to 1-InsP7 and InsP8 respectively. Stephen Shears's laboratory reported in this issue of the Biochemical Journal that PPIP5K1's unexpectedly high affinity for PtdIns(3,4,5)P3, which is synthesized at the plasma membrane, provides a recruitment mechanism for this enzyme in response to growth factor receptor activation. In competition experiments, they observed that PtdIns(3,4,5)P3 binding to PPIP5K1 could be displaced by inositol pyrophosphates and that PPIP5K1 substrates were more potent inhibitors than PPIP5K1 products. Those findings reveal a mechanism for localized depletion of InsP6 and 5-InsP7 at the plasma membrane and further translocation of PtdIns(3,4,5)P3-binding PH-domain-containing proteins.
authors.affiliation: Interdisciplinary Research Institute IRIBHM, Université libre de Bruxelles ULB, Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium. cerneux@ulb.ac.be
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
authors.forename: William's
authors.initials: W
authors.lastname: Elong Edimo
mesh_terms: D000818:Animals; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*
chemical_list: D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D017856:Phosphotransferases (Phosphate Group Acceptor); C519580:PPIP5K1 protein, human