Chemoattractant-mediated transient activation and membrane localization ofAkt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium

Chemotaxis-competent cells respond to a variety of ligands by activating se cond messenger pathways leading to changes in the actin/myosin cytoskeleton and directed cell movement, We demonstrate that Dictyostelium Akt/PKB, a h omologue of mammalian Akt/PKB, is very rapidly and transiently activated by the chemoattractant cAMP, This activation takes place through G protein-co upled chemoattractant receptors via a pathway that requires homologues of m ammalian p110 phosphoinositide-3 kinase. pkbA null cells exhibit aggregatio n-stage defects that include aberrant chemotaxis, a failure to polarize pro perly in a chemoattractant gradient and aggregation at low densities. Mecha nistically, we demonstrate that the PH domain of Akt/PKB fused to GFP trans iently translocates to the plasma membrane in response to cAMP with kinetic s similar to those of Akt/PKB kinase activation and is localized to the lea ding edge of chemotaxing cells in vivo. Our results indicate Akt/PKB is par t of the regulatory network required for sensing and responding to the chem oattractant gradient that mediates chemotaxis and aggregation.