Elevated levels of PtdIns5P in NPM-ALK transformed cells: implication of PIKfyve

Biochem Biophys Res Commun. 2008 Jul 25;372(2):351-5. doi: 10.1016/j.bbrc.2008.05.062. Epub 2008 May 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol Phosphates / analysis
  • Phosphatidylinositol Phosphates / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 5-phosphate
  • Phosphatidylinositol 3-Kinases
  • p80(NPM-ALK) protein
  • Pikfyve protein, mouse
  • Protein-Tyrosine Kinases