Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells

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Abstract
Stimulation of human CD4* T cell lines with interleukin 2 (IL‐2) induces tyrosine, serine and threonine phosphorylation of a series of proteins involved in the IL‐2 receptor (IL‐2R) signaling pathway. Here, we examined whether IL‐2 induces changes in the activity of protein serine/threonine phosphatases in antigen specific, CD4* human T cell lines. Using inhibitors of protein phosphatases 1 (PP1), PP2A, and PP2B, we provide evidence, that IL‐2 induces a downregulation of PP activity in the cytoplasmic/membrane fraction. Thus, IL‐2R ligation for 30 min triggers a 16 percent decrease in total PP2A activity (pn=17) and a seven percent decrease in PP1 activity (pn=17). Cytokine‐induced downregulation of PP2A activity reaches a maximum 60 min after IL‐2R ligation, and returns to baseline levels within two hours. Downregulation of PP1 activity reaches a maximum after 30 min and is largely reversed one hour after IL‐2 stimulation. As determined from immunoblotting experiments using a specific anti‐PP1 or anti‐PP2A antibody, the amount of PP1 and PP2A recovered from cytosolic/membrane fraction remains unchanged after IL‐2 treatment suggesting that the drop in PP1/PP2A activity might be due to a regulatory change rather than to a change in the amount of PP1 and PP2A. In conclusion, we provide evidence, for the first time, that IL‐2 induces a transient downregulation of PP2A activity in T cells. In addition, our findings indicate that cytoplasmic PPl activity is transiently downregulated following IL‐2R ligation in antigen‐specific, human CD4* T cells.