Protein phosphorylation is an essential part of the activating and regulatory processes in the functioning and responses for a variety of cells. Attention has been paid to protein phosphorylation in neutrophils because of the importance of this leukocyte in defense against infection and in a number of allergic and nonallergic tissue-damaging inflammatory reactions. The ultimate purpose of the proposed investigation is to identify, isolate and characterize those proteins which are phosphorylated when neutrophils are stimulated by chemotactic factors and the respective protein kinases for which they are responsible. Attempts will be made to identify the function of the phosphorylated proteins, the role that phosphorylation plays in these respective functions and what role the proteins and their phosphorylation play in neutrophil stimulus response coupling. For these purposes, the following specific aims are proposed. 1) To continue to define the varieties of protein kinases, (tyrosine protein kinase, histone H4 protein kinase, protein kinase C and others) the regulation and the mechanism of activation of kinases and their respective substrates in various subcellular fractions of neutrophils. 2) To continue to define the phosphoproteins, the phosphorylation levels of which are regulated by chemotactic factors (fmet-Leu-Phe) and phorbol ester (PMA) in intact neutrophils. 3) To identify and characterize the molecular components (protein kinases and their substrates) of the physiologically important phosphorylation systems in neutrophils. 4) To study the possible role of phosphorylation and regulation of various protein components involved in superoxide production.
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