aPKCζ affects directed cell migration through the regulation of myosin light chain phosphorylation

Cell motility is an essential cellular process for a variety of biological events. It requires cross-talk between the signaling and the cytoskeletal systems. Despite the recognized importance of aPKC zeta for cell motility, there is little understanding of the mechanism by which aPKC zeta mediates extracellular signals to the cytoskeleton. In the present study, we report that aPKC zeta is required for the cellular organization of acto-non-muscle myosin II (NMII) cytoskeleton, for proper cell adhesion and directed cell migration. We show that aPKCz mediates EGF-dependent RhoA activation and recruitment to the cell membrane. We also show that aPKCz mediates EGF-dependent myosin light chain (MRLC) phosphorylation that is carried out by Rho-associated protein kinase (ROCK), and that aPKC zeta is required for EGF-dependent phosphorylation and inhibition of the myosin phosphatase targeting subunit (MYPT). Finally, we show that aPKCz mediates the spatial organization of the acto-NMII cytoskeleton in response to EGF stimulation. Our data suggest that aPKC zeta is an essential component regulator of acto-NMII cytoskeleton organization leading to directed cell migration, and is a mediator of the EGF signal to the cytoskeleton.