phosphatidylinositol-5-phosphate and Cell-Transformation--Neoplastic

Although guanine nucleotides are essential for cell growth, how their levels are sensed in mammalian cells is unknown. Sumita et al. show that PIP4K2B, a phosphoinositide kinase, is a molecular sensor that transduces changes in GTP into changes in the levels of the phosphoinositide PtdIns5P to modulate tumour cell growth.

Topics: Adenosine Triphosphate; Animals; Binding Sites; Cell Line, Transformed; Cell Proliferation; Cell Transformation, Neoplastic; Fibroblasts; Gene Expression Regulation, Neoplastic; Guanosine Triphosphate; Humans; Isoenzymes; Kinetics; Mice; Mice, Nude; Mutation; Phosphatidylinositol Phosphates; Phosphotransferases (Alcohol Group Acceptor); Protein Binding; Signal Transduction

Phosphatidylinositol 5-monophosphate (PtdIns5P), one of the latest phosphoinositides discovered, has been suggested to play important cellular functions. Here, we report the presence of higher levels of this lipid in cells expressing the oncogenic tyrosine kinase nucleophosmin anaplastic lymphoma kinase (NPM-ALK), a chimeric protein found in the large majority of anaplastic large cell lymphomas (ALCLs). In addition, we describe that a pool of PtdIns5P is located in the membrane extensions characteristic of NPM-ALK-transformed cells. Finally, we show that the increase of PtdIns5P is controlled by the kinase PIKfyve, which is known for its role in vesicular trafficking. These data suggest for the first time a role of PtdIns5P and PIKfyve in oncogenesis, potentially linking intracellular trafficking to cancer.

Topics: Animals; Cell Transformation, Neoplastic; Humans; Mice; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Protein-Tyrosine Kinases