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Chemoattractant‐mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium
Author(s) -
Meili Ruedi,
Ellsworth Charlene,
Lee Susan,
Reddy T.B.K.,
Ma Hui,
Firtel Richard A
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.8.2092
Subject(s) - chemotaxis , protein kinase b , biology , microbiology and biotechnology , dictyostelium , actin cytoskeleton , signal transduction , pi3k/akt/mtor pathway , proto oncogene proteins c akt , cytoskeleton , receptor , biochemistry , cell , gene
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.