title: Effect of lipopolysaccharide on mitogen-activated protein kinases and cytosolic phospholipase A2.
abstract: The addition of platelet-activating factor (PAF) to human neutrophils increases phosphorylation on tyrosine residues and stimulates the activity of p42erk2 mitogen-activated protein kinase (MAP kinase). This action is rapid and transient. In contrast, p42erk2, p44erk1 and the p40hera MAP kinase isoforms are all not tyrosine phosphorylated or activated in human neutrophils stimulated with low concentrations of lipopolysaccharide (LPS) in combination with serum. In spite of this, the PAF-induced tyrosine phosphorylation and activation of the p42erk2 MAP kinase are greatly potentiated in cells pretreated with LPS. More interestingly, although low concentrations of LPS do not affect MAP kinase isoforms in these cells, they cause the phosphorylation of cytosolic phospholipase A2 (cPLA2), as evidenced by a decrease in the electrophoretic mobility of the enzyme. In addition, this stimulus-induced upward shift in the mobility of the enzyme is not inhibited by the tyrosine kinase inhibitor, genistein. Furthermore, LPS increases the release of arachidonic acid in control and PAF-stimulated human neutrophils. These observations clearly show that cPLA2 can be phosphorylated and activated by kinases other than the currently known MAP kinases. It is proposed that there are MAP kinase-dependent and -independent mechanisms for the phosphorylation of cPLA2.
authors.affiliation: Department of Physiology, University of Connecticut Health Center, Farmington 06030, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Fouda
authors.forename: T F
authors.initials: TF
authors.lastname: Molski
authors.forename: M S
authors.initials: MS
authors.lastname: Ashour
authors.forename: R I
authors.initials: RI
authors.lastname: Sha'afi
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D019833:Genistein; D006801:Humans; D015151:Immunoblotting; D007529:Isoflavones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007529:Isoflavones; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2