Phosphoinositide-3-Kinase Catalytic Alpha Polypeptide (PIK3Ca)

The 85-kD subunit lacks PI3-kinase activity and acts as an adaptor, coupling the 110-kD subunit (p110) to activated protein tyrosine kinases. the cDNA for p110 predicts a 1,068-amino acid protein related to a protein which in S. cerevisiae is involved in the sorting of proteins to the vacuole. In COS-1 cells, p110 was catalytically active only when complexed with p85-alpha. PIP3, in turn, is required for translocation of protein kinase B (AKT1, PKB) to the cell membrane, where it is phosphorylated and activated by upstream kinases. The caspase-9-specific inhibitor ZVAD blocked PTEN-induced cell death without altering the effect of PTEN on cell cycle distribution. Overexpression of dominant-negative Akt induced more cell death but had less effect on the cell cycle than overexpression of PTEN.