Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes

The SH2 domain-containing inositol 50-phosphatase (SHIP) negatively regulates antigen, cytokine, and Fc receptor signaling pathways in immune cells. Our knowledge of the function of SHIP largely derives from in vitro studies that utilized SHIP-deficient cell lines and immune cells isolated from SHIP null mice. To avoid the pleiotropic effects observed in mice with germline deletion of SHIP, we have used the Cre-lox system to generate SHIP conditional knockout mice with deletion in specific immune cell populations. In this review we summarize our observations from mice with deletion of SHIP in lymphocyte and macrophage lineages and contrast them with earlier data gathered by the analysis of SHIP null mice.