Structural effects of oncogenic PI3Kα mutations

Sandra B. Gabelli, Chuan Hsiang Huang, Diana Mandelker, Oleg Schmidt-Kittler, Bert Vogelstein, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Physiological activation of PI3Kα is brought about by the release of the inhibition by p85 when the nSH2 binds the phosphorylated tyrosine of activated receptors or their substrates. Oncogenic mutations of PI3Kα result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival. Structural information suggests that some mutations also activate the enzyme by releasing p85 inhibition. Other mutations work by different mechanisms. For example, the most common mutation, His1047Arg, causes a conformational change that increases membrane association resulting in greater accessibility to the substrate, an integral membrane component. These effects are examples of the subtle structural changes that result in increased activity.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalCurrent topics in microbiology and immunology
Issue number1
StatePublished - 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)


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