The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations
- 14 December 2007
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 318 (5857), 1744-1748
- https://doi.org/10.1126/science.1150799
Abstract
PIK3CA , one of the two most frequently mutated oncogenes in human tumors, codes for p110α, the catalytic subunit of a phosphatidylinositol 3-kinase, isoform α (PI3Kα, p110α/p85). Here, we report a 3.0 angstrom resolution structure of a complex between p110α and a polypeptide containing the p110α-binding domains of p85α, a protein required for its enzymatic activity. The structure shows that many of the mutations occur at residues lying at the interfaces between p110α and p85α or between the kinase domain of p110α and other domains within the catalytic subunit. Disruptions of these interactions are likely to affect the regulation of kinase activity by p85 or the catalytic activity of the enzyme, respectively. In addition to providing new insights about the structure of PI3Kα, these results suggest specific mechanisms for the effect of oncogenic mutations in p110α and p85α.Keywords
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