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| The EMBO Journal
(1999) 18, 2092–2105, doi:10.1093/emboj/18.8.2092 |
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| Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium |
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| Ruedi Meili, Charlene Ellsworth, Susan Lee, T.B.K. Reddy, Hui Ma and Richard A Firtel |
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Department of Biology, Center for Molecular Genetics, Room 225, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA To whom correspondence should be addressed Richard A Firtel, rafirtel@ucsd.edu Received 14 December 1998; Revised 24 February 1999; Accepted 24 February 1999. |
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| Abstract |
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| 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. |
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| Keywords: Akt–PKB, chemotaxis, Dictyostelium, PI3 kinase |
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