Mol Cell Biol. 2014; 34 (18): 3359-3373.

Pérez-García V, Redondo-Muñoz J, Kumar A, Carrera AC.

The PI3K/PTEN (phosphoinositide 3-kinase/phosphatase and tensin homolog) pathway is one of the central routes that enhances cell survival, division and migration, and is frequently deregulated in cancer. The PI3K catalyze formation of phosphatidylinositol (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 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 PI3K dimerize in vivo, and that PI3K and PTEN activities modulate each other in a complex that controls cell PI(3,4,5)P₃ levels.