Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10766056 | Biochemical and Biophysical Research Communications | 2009 | 5 Pages |
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.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Claire Chaussade, Kitty Cho, Claire Mawson, Gordon W. Rewcastle, Peter R. Shepherd,