The requirement of both extracellular regulated kinase and p38 mitogen-activated protein kinase for stimulation of cytosolic phospholipase A(2) activity by either FcgammaRIIA or FcgammaRIIIB in human neutrophils. A possible role for Pyk2 but not for the Grb2-Sos-Shc complex.
The signal transduction pathways initiated by opsonized zymosan (OZ) leading to activation of cytosolic phospholipase A(2) (cPLA(2)) in human neutrophils remain obscure. In a previous study, we showed that the activation of cPLA(2) by OZ is tyrosine kinase-dependent. The present study demonstrates that the signals initiated by OZ involve activation of tyrosine kinase Pyk2 but not the formation of the adhesion protein complex, Shc-Grb2-Sos. Stimulation of cPLA(2) activity by OZ is mediated by Fc gamma receptors (FcgammaRs) and not by complement receptors for the C3b protein. Cross-linking of FcgammaRIIA or FcgammaRIIIB induces p38 mitogen-activated protein (MAP) kinase and extracellular regulated kinase (ERK) phosphorylation. The kinetics of cPLA(2) activity stimulated by either of the FcgammaRs or by both is similar to that of p38 MAP kinase and was detected as early as 15 s after stimulation, maintained a plateau for 10 min, and decreased thereafter. ERK activation was detected also within 15 s but decreased significantly 5 min after stimulation. The MEK inhibitor, PD-098059, or the p38 MAP kinase inhibitor, SB-203580, caused a partial inhibition during the time course of cPLA(2) activity, whereas their combination caused a total inhibition. Thus, although ERK activation is significantly shorter than that of p38 MAP kinase, it is equally required for activation and maintenance of cPLA(2) activity by occupancy of a single receptor, FcgammaRIIA or FcgammaRIIIB.
Hazan-Halevy
I
I
Laboratory of Infectious Diseases, Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center, Beer Sheva 84105, Israel.
Seger
R
R
Levy
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D015703:Antigens, CD / Q000502:physiology*; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D008954:Models, Biological; D009504:Neutrophils / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D015703:Antigens, CD; D004791:Enzyme Inhibitors; C080568:Fc gamma receptor IIA; C080571:Fc gamma receptor IIB; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D017452:Receptors, IgG; D013481:Superoxides; D014443:Tyrosine; D015054:Zymosan; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one