Article
Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α (PIK3CA).
Proceedings of the National Academy of Sciences of the United States of America - 18 Sept 2012
Burke John E, Perisic Olga, Masson Glenn R, Vadas Oscar, Williams Roger L
Abstract excerpt
The p110α catalytic subunit (PIK3CA) is one of the most frequently mutated genes in cancer. We have examined the activation of the wild-type p110α/p85α and a spectrum of oncogenic mutants using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We find that for the wild-type enzyme, the natural transition from an inactive cytosolic conformation to an activated form on membranes entails four distinct events....
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