The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide.

The monosaccharide lipid A precursor, N2,O3-diacylglucosamine 1-phosphate (Escherichia coli lipid X), has been shown previously to be a potent B-lymphocyte mitogen. We now report that lipid X interacts with macrophages, stimulating turnover of phosphatidylinositol, deacylation of phospholipids, and release of arachidonic acid. In addition, the monosaccharide lipid X, the incomplete lipid A disaccharides found in KDO-deficient mutants, and crude free lipid A by itself activate protein kinase C isolated from RAW 264.7 macrophages. This activation is augmented by diglyceride, a product of phosphatidylinositol turnover. Like the lipid X-induced mitogenesis of B-lymphocytes, lipid X activation of macrophages and the cell-free activation of protein kinase by lipid X require the presence of the O-linked hydroxymyristoyl residue at position 3. We suggest, therefore, that some of the biological effects of lipid A may be mediated by its interaction with protein kinase C.