title: SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells.
abstract: Phosphoinositides, particularly phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], are recognized by SHIP2 (also known as INPPL1) a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the preferred SHIP2 substrate is PI(3,4,5)P3, PI(4,5)P2 can also be dephosphorylated by this enzyme to phosphatidylinositol 4-phosphate (PI4P). Through depletion of SHIP2 in the glioblastoma cell line 1321 N1, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In 1321 N1 cells, the PI(4,5)P2-binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls 1321 N1 cell migration through the organization of focal adhesions. Thus, our results reveal a new role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma 1321 N1 cells.
authors.affiliation: IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, Bruxelles B-1070, Belgium.
authors.forename: William's
authors.initials: W
authors.lastname: Elong Edimo
authors.affiliation: IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, Bruxelles B-1070, Belgium.
authors.forename: Somadri
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Protein Phosphorylation & Proteomics Lab, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium.
authors.forename: Rita
authors.initials: R
authors.lastname: Derua
authors.affiliation: Protein Phosphorylation & Proteomics Lab, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Janssens
authors.affiliation: Protein Phosphorylation & Proteomics Lab, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Herestraat 49 PO-box 901, Leuven B-3000, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.affiliation: Laboratory of Neurophysiology, ULB Bâtiment C, 808 route de Lennik, Bruxelles B-1070, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vanderwinden
authors.affiliation: Génétique Humaine, GIGA center, Ulg, B-4000 Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Robe
authors.affiliation: IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, Bruxelles B-1070, Belgium cerneux@ulb.ac.be.
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Cell migration; Focal adhesion; Phosphoinositide; SHIP2