Involvement of Multiple Kinases in Neutrophil Activation

Production of reactive oxygen metabolites by the NADPH oxidase is an essential mechanism underlying the microbicidal role of phagocytes. Receptor-mediated activation of the oxidase was originally thought to be mediated by calcium and/or by protein kinase C (PKC). However, recent evidence suggests that additional signalling pathways exist. In this article the possible role of tyrosine phosphorylation is discussed. In addition, results obtained using an in vitro kinase renaturation assay are described. The latter assay revealed the existence of at least four serine/threonine kinases that are activated in cells stimulated with chemoattractants. One of these, of molecular weight 41,000 was identified as a member of the ERK or MAP-kinase family. The existence of multiple, possibly redundant or synergistic signaling pathways is considered.