Phosphatidylinositol Signaling Visualized in T cells

Abstract

Two groups used pleckstrin homology domains, which bind to phosphatidylinositol (PI) lipids, fused to green fluorescent protein (GFP) to monitor the activation of phosphatidylinositol 3-kinase (PI3K) in activated T cells. Harriague and Bismuth showed rapid production of PI3,4,5,P3 in cultured T cells (on the basis of redistribution of either an Akt-GFP fusion protein or Gab-1-GFP fusion protein to the plasma membrane) in response to interaction with antigen-presenting cells (APCs). Pharmacological inhibition of PI3K blocked redistribution of the fusion proteins, but did not affect T cell activation-induced calcium signals or interleukin 2 production. Costello et al. created transgenic mice expressing an Akt-GFP fusion protein and analyzed PI3K activity during activation of T cells from these mice. They also found that interaction with APCs promoted the accumulation of the fusion protein at the site of T cell-APC contact (the so-called immune synapse). In addition, both groups reported dynamic recruitment of the fusion proteins to the plasma membrane outside the immune synapse. Costello et al. observed that the production of 3-phosphorylated PI lipids persisted over several hours and that pharmacological inhibition of PI3K resulted in the inability of the T cells to proliferate in response to stimulation. Thus, PI3K signaling may not be essential for the early responses to T cell receptor ligation, but may be part of the sustained signaling system that controls T cell proliferation. The function of PI3K signaling outside the immune synapse and how that signal is activated remain to be determined (see Shaw). J. Harriague, G. Bismuth, Imaging antigen-induced PI3K activation in T cells. Nature Immunol. 3, 1090-1096 (2002). [Online Journal]P. S. Costello, M. Gallegher, D. A. Cantrell, Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse. Nature Immunol. 3, 1082-1089 (2002). [Online Journal]A. S.-Y. Shaw, Slick signaling. Nature Immunol. 3, 1058-1059 (2002). [Online Journal]