Activation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK.
Incubation of human neutrophils with FMLP, a chemotactic peptide, or PMA, a stimulator of protein kinase C, resulted in the activation of p38, a proline-directed kinase. Previous studies had shown that extracellular signal-regulated kinase (ERK), another proline-directed kinase, was activated with similar kinetics in neutrophils stimulated with FMLP and PMA (1, 2). Because one possible target for these proline-directed kinases is p47phox, a component of the respiratory burst oxidase, we examined the phosphorylation of this protein by p38 and ERK, as well as JNK, another proline-directed kinase present in neutrophils. We found that both p38 and ERK phosphorylated p47phox at the same site and at similar rates, but that p47phox was not a substrate for JNK. These data show that p38, like ERK, can be activated in neutrophils exposed to an appropriate stimulus, and that some but not all proline-directed kinases are able to participate in the phosphorylation of a protein essential for normal neutrophil function.
El Benna
J
J
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Han
J
J
Park
J W
JW
Schmid
E
E
Ulevitch
R J
RJ
Babior
B M
BM
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000097:blood*; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000097:blood; D019255:NADPH Oxidases; D009419:Nerve Tissue Proteins / Q000097:blood*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000737:chemistry; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation; D011494:Protein Kinases / Q000097:blood*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D036143:Receptor, EphA8; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036143:Receptor, EphA8; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate