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

• Published in: The EMBO journal Vol. 18; no. 8; pp. 2092 - 2105
• Main Authors: Meili, R, Ellsworth, C, Lee, S, Reddy, T.B.K, Ma, H, Firtel, R.A
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.04.1999; Blackwell Publishing Ltd
• Subjects: Akt-PKB; Amino Acid Sequence; Animals; Base Sequence; Biological Transport; cell aggregaton; Cell Membrane - metabolism; Chemotactic Factors - pharmacology; Chemotaxis; cyclic AMP; Cyclic AMP - pharmacology; cytochemistry; Dictyostelium; Dictyostelium - drug effects; Dictyostelium - metabolism; Dictyostelium discoideum; DNA Primers; Enzyme Activation; Green Fluorescent Proteins; Luminescent Proteins - genetics; Mammals; Molecular Sequence Data; Phosphatidylinositol 3-Kinases - metabolism; PI3 kinase; plasma membrane; protein transport; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.8.2092

Chemotaxis‐competent cells respond to a variety of ligands by activating second messenger pathways leading to changes in the actin/myosin cytoskeleton and directed cell movement. We demonstrate that Dictyostelium Akt/PKB, a homologue of mammalian Akt/PKB, is very rapidly and transiently activated by the chemoattractant cAMP. This activation takes place through G protein‐coupled chemoattractant receptors via a pathway that requires homologues of mammalian p110 phosphoinositide‐3 kinase. pkbA null cells exhibit aggregation‐stage defects that include aberrant chemotaxis, a failure to polarize properly in a chemoattractant gradient and aggregation at low densities. Mechanistically, we demonstrate that the PH domain of Akt/PKB fused to GFP transiently translocates to the plasma membrane in response to cAMP with kinetics similar to those of Akt/PKB kinase activation and is localized to the leading edge of chemotaxing cells in vivo. Our results indicate Akt/PKB is part of the regulatory network required for sensing and responding to the chemoattractant gradient that mediates chemotaxis and aggregation.