PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac.

Fcgamma receptor-mediated phagocytosis is a model for the study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is known of the role of lipid phosphatases in the control of ITAM signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the dual-specificity phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in the signal transduction pathway leading to Fcgamma receptor IIA-mediated phagocytosis and the activation of Rac. The expression of wildtype PTEN completely abrogated the phagocytosis of immunoglobulin-G-sensitized sheep red blood cells, as compared with the catalytically inactive mutant of PTEN, which had no effect. This is the first direct evidence that PTEN, an inositol 3' phosphatase, regulates Fcgamma receptor-mediated phagocytosis, an ITAM-based signaling event. The data suggest that PTEN exerts control over phagocytosis potentially by controlling the downstream conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac following ITAM stimulation.