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.