Uncovering the PI3Ksome: Phosphoinositide 3-Kinases and Counteracting PTEN Form a Signaling Complex with Intrinsic Regulatory Properties |
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| Authors: | Claire Conche Karsten Sauer |
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| Institution: | aDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA ;bDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA |
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| 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.” |
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