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

Abstract

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.”

This article is related to:

Cell Activation-Induced Phosphoinositide 3-Kinase Alpha/Beta Dimerization Regulates PTEN Activity

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The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

ACKNOWLEDGMENTS

Our work is supported by NIH grants GM100785, GM065230, and 5UL1TR001114 and by The Leukemia and Lymphoma Society Scholar Award 1440-11 to K.S.