p90-RSK and Akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils

Abstract

Stimulation of neutrophils with the chemoattractant fMet-Leu-Phe (fMLP) triggers phosphorylation/inactivation of the a- and beta-isoforms of glycogen synthase kinase 3 (GSK-3) with phosphorylation of the alpha-isoform predominating. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively. Inhibitor studies indicated that phosphorylation of GSK-3alpha may be catalyzed by the combined action of p90-RSK and Akt and may represent a new strategy by which G protein-coupled receptors inactivate GSK-3. Inactivation of GSK-3 may be one of the mechanisms that delay apoptosis in fMLP-stimulated neutrophils.