A hypothetic model of aPKC PM targeting and kinase activation. (A) Free cytosolic aPKC in autoinhibited conformation has polybasic PSr blocked by the KD from binding to PM. Binding of Par-6 to aPKC induces conformation changes that expose the PSr in aPKC and allow the C-terminus of Par-6 to simultaneously inhibit the aPKC KD. (B) Polybasic PSr in aPKC/Par-6 complex binds to PM via electrostatic interaction with PI4P and PIP₂, which are uniquely enriched on PM. (C) Intracellular domain of apical polarity protein Crb interacts with the C-terminal PDZ domain of Par-6 and releases its inhibition on aPKC KD. Interaction with Crb could also facilitate the apical enrichment of PM-bound aPKC/Par-6 in cells. (D) Activated aPKC phosphorylates Lgl to prevent it from binding to apical PM. Illustration is based on Drosophila epithelial cells. AJ, adherens junction.