Human tumor mutants in the p110α subunit of PI3K

The PI3K-Akt pathway is frequently upregulated in human tumors. Recently, somatic mutations of PIK3CA, encoding p110 alpha catalytic subunit of Class IA PI3Ks, have been found in various cancers. The two most common types of p110 alpha mutants, those in the helical and kinase domains, have been shown to be very potent in Akt activation and oncogenic transformation by several groups. Notably these common mutations may not enhance recruitment of p110 alpha to the plasma membrane where its substrates are located. We have investigated the effect of membrane localization on common PIK3CA tumor mutants via myristoylation. In addition we have studied a third class of less frequent mutants in the p85-binding domain, in an attempt to gain insight into p85's inhibitory effect on p110 alpha. This article briefly reviews and extends the literature on mutant forms of p110 alpha.