title: The influence of anionic lipids on SHIP2 phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase activity.
abstract: The SH2 domain containing inositol 5-phosphatase 2 (SHIP2) catalyzes the dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P(2)) and participates in the insulin signalling pathway in vivo. In a comparative study of SHIP2 and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), we found that their lipid phosphatase activity was influenced by the presence of vesicles of phosphatidylserine (PtdSer). SHIP2 PtdIns(3,4,5)P(3) 5-phosphatase activity was greatly stimulated in the presence of vesicles of PtdSer. This effect appears to be specific for di-C8 and di-C16 fatty acids of PtdIns(3,4,5)P(3) as substrate. It was not observed with inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P(4)) another in vitro substrate of SHIP2, nor with Type I Ins(1,4,5)P(3)/Ins(1,3,4,5)P(4) 5-phosphatase activity, an enzyme which acts on soluble inositol phosphates. Vesicles of phosphatidylcholine (PtdCho) stimulated only twofold PtdIns(3,4,5)P(3) 5-phosphatase activity of SHIP2. Both a minimal catalytic construct and the full length SHIP2 were sensitive to the stimulation by PtdSer. In contrast, PtdIns(3,4,5)P(3) 5-phosphatase activity of the Skeletal muscle and Kidney enriched Inositol Phosphatase (SKIP), another member of the mammaliam Type II phosphoinositide 5-phosphatases, was not sensitive to PtdSer. Our enzymatic data establish a specificity in the control of SHIP2 lipid phosphatase activity with PtdIns(3,4,5)P(3) as substrate which is depending on the fatty acid composition of the substrate.
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université libre de Bruxelles, Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Vandeput
authors.forename: Katrien
authors.initials: K
authors.lastname: Backers
authors.forename: Vincent
authors.initials: V
authors.lastname: Villeret
authors.forename: Xavier
authors.initials: X
authors.lastname: Pesesse
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
mesh_terms: D002384:Catalysis; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010718:Phosphatidylserines / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D018129:Phosphatidylinositol Phosphates; D010718:Phosphatidylserines; D011993:Recombinant Fusion Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; D005982:Glutathione Transferase; C471548:SKIP enzyme, human; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases