Pathway of phosphatidylinositol(3,4,5)-trisphosphate synthesis in activated neutrophils

Abstract

Neutrophils activated by the formyl peptide f-Met-LeuPhe transiently accumulate a small subset of highly polar inositol lipids. A similar family of lipids also appear in many other cells in response to a range of growth factors and activated oncogenes, and are presumed to be the direct or indirect products of 3-phosphatidylinositol kinase. The structures of these lipids are shown to be phos-phatidylinositol 3-phosphate, phosphatidylinositol-(3,4)bisphosphate and phosphatidylinositol-(3,4,5)trisphosphate, and we present evidence that in intact neutrophils a phosphatidylinositol-(4,5)bisphosphate-3-kinase seems to be the focal point through which agonists stimulate the formation of 3-phosphorylated inositol lipids.