title: SHIP2 multiple functions: a balance between a negative control of PtdIns(3,4,5)P₃ level, a positive control of PtdIns(3,4)P₂ production, and intrinsic docking properties.
abstract: The SH2 domain containing inositol 5-phosphatase 2 (SHIP2) belongs to the family of the mammalian inositol polyphosphate 5-phosphatases. The two closely related isoenzymes SHIP1 (or SHIP) and SHIP2 contain a N-terminal SH2 domain, a catalytic domain, potential PTB domain-binding sites (NPXY), and C-terminal proline-rich regions with consensus sites for SH3 domain interactions. In addition, SHIP2 contains a unique sterile alpha motif (SAM) domain that could be involved in SAM-SAM domain interactions with other proteins or receptors. SHIP2 also shows the presence of an ubiquitin interacting motif at the C-terminal end. SHIP2 is essentially a PI(3,4,5)P(3) 5-phosphatase that negatively controls PI(3,4,5)P(3) levels in intact cells and produce PI(3,4)P(2) . Depending on the cells and stimuli, PI(3,4)P(2) could accumulate at important levels and be a "second messenger" by its own. It could interact with a very large number of target proteins such as PKB or TAPP1 and 2 that control insulin sensitivity. In addition to its catalytic activity, SHIP2 is also a docking protein for a large number of proteins: Cytoskeletal, focal adhesion proteins, scaffold proteins, adaptors, protein phosphatases, and tyrosine kinase associated receptors. These interactions could play a role in the control of cell adhesion, migration, or endocytosis of some receptors. SHIP2 could be acting independently of its phosphatase activity being part of a protein network of some receptors, e.g., the EGF receptor or BCR/ABL. These non-catalytic properties associated to a PI phosphatase have also been reported for other enzymes of the metabolism of myo-inositol such as Ins(1,4,5)P(3) 3-kinases, inositol phosphate multikinase (IPMK), or PTEN.
authors.affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Université Libre de Bruxelles, Campus Erasme, Bldg. C, 808 Route de Lennik, 1070 Brussels, Belgium. cerneux@ulb.ac.be
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
authors.forename: William's Elong
authors.initials: WE
authors.lastname: Edimo
authors.forename: Laurence
authors.initials: L
authors.lastname: Deneubourg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pirson
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; D020794:Receptor Protein-Tyrosine Kinases; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases