Uncovering the PI3Ksome: Phosphoinositide 3-Kinases and Counteracting PTEN Form a Signaling Complex with Intrinsic Regulatory Properties

Abstract

Production of the phosphoinositide lipid PIP3 by class I 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'.