Uncovering the PI3Ksome: phosphoinositide 3-kinases and counteracting PTEN form a signaling complex with intrinsic regulatory properties.

Production of the phosphoinositide lipid phosphatidylinositol (3,4,5)trisphosphate [PI(3,4,5)P3, or PIP3] by class I phosphoinositide 3-kinases (PI3Ks) is a major signaling mechanism whose deregulation contributes to serious diseases, including cancer. New findings suggest that tyrosine kinase receptor engagement results in the assembly of hetero-oligomeric PI3K complexes in which PI3Kα first activates PI3Kβ, and PI3K catalytic activity then promotes recruitment and activation of the PIP3-removing tumor suppressor PTEN. Thus, PIP3 production is fine-tuned through formation of an intrinsically regulated "PI3Ksome."