Article ID Journal Published Year Pages File Type
10766056 Biochemical and Biophysical Research Communications 2009 5 Pages PDF
Abstract
PIK3CA codes for the p110α isoform of class-IA PI 3-kinase and oncogenic mutations in the helical domain and kinase domain are common in several cancers. We studied the biochemical properties of a common helical domain mutant (E545K) and a common kinase domain mutant (H1047R). Both retain the ability to autophosphorylate Ser608 of p85α and are also inhibited by a range of PI 3-kinase inhibitors (Wortmannin, LY294002, PI-103 and PIK-75) to a similar extent as WT p110α. Both mutants display an increased Vmax but while a PDGF derived diphosphotyrosylpeptide caused an increase in Vmax for WT p85α/p110α it did not for the E545K variant and actually decreased Vmax for the H1047R variant. Further, the E545K mutant was activated by H-Ras whereas the H1047R mutant was not. Together these results suggest helical domain mutants are in a state mimicking activation by growth factors whereas kinase domain mutants mimic the state activated by H-Ras.
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Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
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