title: How does SHIP1/2 balance PtdIns(3,4)P2 and does it signal independently of its phosphatase activity?
abstract: The number of cellular events identified as being directly or indirectly modulated by phosphoinositides dramatically increased in the recent years. Part of the complexity results from the fact that the seven phosphoinositides play second messenger functions in many different areas of growth factors and insulin signaling, cytoskeletal organization, membrane dynamics, trafficking, or nuclear signaling. PtdIns(3,4)P2 is commonly reported as a product of the SH2 domain-containing inositol 5-phosphatases 1/2 (SHIP1 and SHIP2) that dephosphorylate PtdIns(3,4,5)P3 at the 5-position. Here we discuss recent interest in PtdIns(3,4)P2 signaling highlighting its involvement in key cellular mechanisms such as cell adhesion, migration, and cytoskeletal regulation. We question and discuss the involvement of SHIP2 either as a PI 5-phosphatase or as a scaffold protein in insulin signaling, cytoskeletal dynamics, and endocytosis of growth factor receptors.
authors: Department of Pathophysiology, China Medical University, Heping District, Shenyang Liaoning Province, China.
authors: Jingwei
authors: J
authors: Xie
authors: Christophe
authors: C
authors: Erneux
authors: Isabelle
authors: I
authors: Pirson
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D007328:Insulin / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D010766:Phosphorylation; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D025801:Ubiquitin; C060980:phosphatidylinositol 3,4-diphosphate; D066246:ErbB Receptors; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: EGFR endocytosis; PtdIns(3,4)P2; SHIP1/2; mono-ubiquitination; scaffold properties