Chimeric receptors composed of phosphoinositide 3-kinase domains and FCgamma receptor ligand-binding domains mediate phagocytosis in COS fibroblasts.

Receptors for the Fc portion of IgG (FcgammaR) initiate phagocytosis of IgG-opsonized particles by a process involving the assembly of a multi-molecular signaling complex. Several members of this complex have been identified, including Src family kinases, Syk/ZAP 70 family kinases, and phosphoinositide 3-kinase (PI3-K). To test directly the role of PI3-K in mediating phagocytosis, we assessed the phagocytic ability of chimeric receptors composed of FcgammaR extracellular and transmembrane domains fused to regions of the p85 subunit of PI3-K. We found that chimeric receptors with cytoplasmic tails composed of the entire p85 subunit of PI3-K or the inter-Src homology 2 portion of p85 triggered phagocytosis in transfected COS fibroblasts. These two chimeras also showed phosphoinositide kinase activity in vitro when immunoadsorbed. In contrast, a chimera containing only the carboxyl-terminal Src homology 2 domain of p85 that does not interact with the catalytic p110 subunit of PI3-K did not trigger phagocytosis, nor did it show kinase activity in vitro. These data suggest that localization and direct activation of PI3-K at the site of particle attachment is sufficient to trigger the process of phagocytosis.