p90-RSK and Akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils.
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.
De Mesquita
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DD
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhan
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Crossley
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Badwey
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JA
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D002630:Chemotactic Factors; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D011518:Proto-Oncogene Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D038341:Glycogen Synthase Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin