title: Cell activation-induced phosphoinositide 3-kinase alpha/beta dimerization regulates PTEN activity.
abstract: The phosphoinositide 3-kinase (PI3K)/PTEN (phosphatase and tensin homolog) pathway is one of the central routes that enhances cell survival, division, and migration, and it is frequently deregulated in cancer. PI3K catalyzes formation of phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] after cell activation; PTEN subsequently reduces these lipids to basal levels. Activation of the ubiquitous p110α isoform precedes that of p110β at several points during the cell cycle. We studied the potential connections between p110α and p110β activation, and we show that cell stimulation promotes p110α and p110β association, demonstrating oligomerization of PI3K catalytic subunits within cells. Cell stimulation also promoted PTEN incorporation into this complex, which was necessary for PTEN activation. Our results show that PI3Ks dimerize in vivo and that PI3K and PTEN activities modulate each other in a complex that controls cell PI(3,4,5)P3 levels.
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, Spain.
authors: Vicente
authors: V
authors: Pérez-García
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, Spain.
authors: Javier
authors: J
authors: Redondo-Muñoz
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, Spain.
authors: Amit
authors: A
authors: Kumar
authors: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Madrid, Spain acarrera@cnb.csic.es.
authors: Ana C
authors: AC
authors: Carrera
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018129:Phosphatidylinositol Phosphates; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051059:PTEN Phosphohydrolase