Characterization of a Tumor-Associated Activating Mutation of the p110β PI 3-Kinase

Hashem A. Dbouk, Bassem D. Khalil, Haiyan Wu, Aliaksei Shymanets, Bernd Nürnberg, Jonathan M. Backer

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


The PI3-kinase pathway is commonly activated in tumors, most often by loss of PTEN lipid phosphatase activity or the amplification or mutation of p110α. Oncogenic mutants have commonly been found in p110α, but rarely in any of the other catalytic subunits of class I PI3-kinases. We here characterize a p110β helical domain mutation, E633K, first identified in a Her2-positive breast cancer. The mutation increases basal p110β activity, but does not affect activation of p85/p110β dimers by phosphopeptides or Gβγ. Expression of the mutant causes increases in Akt and S6K1 activation, transformation, chemotaxis, proliferation and survival in low serum. E633 is conserved among class I PI3 Ks, and its mutation in p110β is also activating. Interestingly, the E633K mutant occurs near a region that interacts with membranes in activated PI 3-kinases, and its mutation abrogates the requirement for an intact Ras-binding domain in p110β-mediated transformation. We propose that the E633K mutant activates p110β by enhancing its basal association with membranes. This study presents the first analysis of an activating oncogenic mutation of p110β.

Original languageEnglish (US)
Article numbere63833
JournalPloS one
Issue number5
StatePublished - May 29 2013

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


Dive into the research topics of 'Characterization of a Tumor-Associated Activating Mutation of the p110β PI 3-Kinase'. Together they form a unique fingerprint.

Cite this