Lipid phosphatases identified by screening a mouse phosphatase shRNA library regulate T-cell differentiation and Protein kinase B AKT signaling

We identified a series of lipid phosphatases that regulate differentiation of naïve CD4 T cells to their major phenotypic states, T-helper (Th)1/Th2/Th17. Previously, phosphatase and tensin homolog (PTEN) was the only lipid phosphatase shown to function in this process. To identify these phosphatases, we used a unique "phosphatase-wide" screening procedure. Our results demonstrate that myotubularin-related protein (MTMR) 9 and MTMR7 play critical roles in Th differentiation. Knocking down MTMR9 enhances Th1 priming, and such Th1 cells show increased protein kinase B (PKB)/AKT phosphorylation. Knocking down MTMR7 increases Th2 and Th17 priming; these cells show enhanced AKT phosphorylation.