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PMID:10205164
| Citation |
Meili, R, Ellsworth, C, Lee, S, Reddy, TB, Ma, H and Firtel, RA (1999) Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium. EMBO J. 18:2092-105 |
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| Abstract |
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. |
| Links |
PubMed PMC1171294 Online version:10.1093/emboj/18.8.2092 |
| Keywords |
Amino Acid Sequence; Animals; Base Sequence; Biological Transport; Cell Membrane/metabolism; Chemotactic Factors/pharmacology; Chemotaxis; Cyclic AMP/pharmacology; DNA Primers; Dictyostelium/drug effects; Dictyostelium/metabolism; Enzyme Activation; Green Fluorescent Proteins; Luminescent Proteins/genetics; Molecular Sequence Data; Phosphatidylinositol 3-Kinases/metabolism; 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 |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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