title: Phosphorylated SHIP2 on Y1135 localizes at focal adhesions and at the mitotic spindle in cancer cell lines.
abstract: The SH2 containing inositol 5-phosphatase SHIP2 is a member of the mammalian phosphoinositide polyphosphate 5-phosphatase family. It is a multi-domain protein comprising a central catalytic domain, an SH2 domain at its N-terminus, proline rich sequences and SAM domain at its C-terminus. It can dephosphorylate both phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P(3)) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) and can participate in multiple signaling events in response to growth factors such as EGF, FGF or PDGF. Human SHIP2 can be phosphorylated at two major tyrosine residues Tyr986 and Tyr1135. Here, we report two intracellular localizations of pSHIP2(Y1135): pSHIP2(Y1135)-ir localizes at focal adhesions in EGF-stimulated HeLa cells and at the mitotic spindle in HeLa, in GIST882 cells, a human model of gastrointestinal stromal tumors derived cells, and in human astrocytoma 1321N1 cells. pSHIP2(Y1135)-ir is maximal at metaphase. In N1 cells, evidence is provided that the SHIP2 pathway impacts the distribution of mitotic centrosomes, particularly ү-tubulin. Our data reinforce the concept that SHIP2 localization in intact cells is dependent on phosphorylation mechanisms on both Ser/Thr and Tyr residues, i.e. Y1135, in three cancer cell lines.
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Deneubourg
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: William's
authors.initials: W
authors.lastname: Elong Edimo
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Colette
authors.initials: C
authors.lastname: Moreau
authors.affiliation: Laboratory of Neurophysiology, Faculty of medicine, Université libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vanderwinden
authors.affiliation: Interdisciplinary Research Institute (IRIBHM), Université libre de Bruxelles (ULB), Campus Erasme, 808 Route de Lennik, 1070 Brussels, Belgium. Electronic address: cerneux@ulb.ac.be.
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
mesh_terms: D000818:Animals; D019556:COS Cells; D018385:Centrosome / Q000378:metabolism*; D002522:Chlorocebus aethiops; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010750:Phosphoproteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D014443:Tyrosine; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Inositol 5-phosphatase; Phosphatidylinositol metabolism; SHIP2 phosphorylation; Signal transduction