Signal transduction by human-restricted Fc gamma RIIa involves three distinct cytoplasmic kinase families leading to phagocytosis

Recent experiments indicate an important role for Src family and Syk protei n tyrosine kinases and phosphatidylinositol 3-kinase in the signal transduc tion process initiated by mouse receptors for IgG and leading to phagocytos is. Considerably less is known regarding signal transduction by the human-r estricted IgG receptor, FcyRIIa. Furthermore, the relationship among the Sr c family, Syk, and phosphatidylinositol 3-kinase in phagocytosis is not und erstood. Here, we show that Fc gamma RIIa is phosphorylated by an Src famil y member, which results in recruitment and concomitant activation of the di stal enzymes Syk and phosphatidylinositol 3-kinase. Using a Fc gamma RI-p85 receptor chimera cotransfected with kinase-inactive mutants of Syk or appl ication of a pharmacological inhibitor of Syk, we show that Syk acts in par allel with phosphatidylinositol 3-kinase. Our results indicate that Fc gamm a RIIa-initiated monocyte or neutrophil phagocytosis proceeds from the clus tered IgG receptor to Src to phosphatidylinositol 3-kinase and Syk.