RRC ID 29105
著者 Meili R, Ellsworth C, Lee S, Reddy TB, Ma H, Firtel RA.
タイトル Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.
ジャーナル EMBO J.
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.
巻・号 18(8)
ページ 2092-105
公開日 1999-4-15
DOI 10.1093/emboj/18.8.2092
PMID 10205164
PMC PMC1171294
MeSH 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
IF 9.792
引用数 333
細胞性粘菌 S00335