PIK3CA and cancer: After the Akt-induced phosphorylation of either Ser21 (α) or Ser9 (β) in N-terminal regulatory domains in response to PI3K-mediated signaling, GSK3 (both GSH3α and GSK3β) is inactivated and targeted for proteasomal degradation.86,90 The Akt-mediated phosphorylation of GSK3 produces an intramolecular pseudosubstrate that blocks the binding pocket and inhibits the substrate from approaching GSK3.91 GSK3 expression affects various biochemical processes in cancer.