Fig. 5.

PIP₃ accumulation and Akt activation in neutrophil polarity. In the model, activated WT neutrophils polarize to form one leading-edge pseudpod enriched in PIP₃ and p55. This accumulation of PIP₃ promotes phosphorylation of Akt. In p55^−/− neutrophils, chemoattractants induce the extension of multiple pseudpods in various directions. PIP₃ aggregates in various locations coinciding with F-actin polymerization, rather than accumulating at one leading edge. PIP₃ has emerged as a critical mediator of pseudopod stability during neutrophil polarization. Because total PIP₃ production is unchanged in the absence of p55, we hypothesize that the polarity and Akt-phosphorylation defects are due to abnormal trafficking or accumulation of PIP₃ at the front of the cell.