Identification of an S100A1/S100B target protein: phosphoglucomutase

Phosphoglucomutase was identified as a potential intracellular S100 target protein because it interacted with two members of the S100 family of calcium-modulated proteins, S100A1 and S100B, in gel overlay experiments. These results were confirmed by affinity chromatography experiments demonstrating that S100A1 and S100B bound to phosphoglucomutase-Sepharose in a calcium-dependent manner. In the reverse experiment, phosphoglucomutase bound to S100A1 and S100B-Sepharose in a calcium-dependent manner. S100A1 inhibited phosphoglucomutase activity in a calcium-dependent manner. In contrast, S100B stimulated phosphoglucomutase activity in a calcium-dependent manner. Other calcium-binding proteins (calmodulin, troponin C, parvalbumin, and alpha-lactalbumin) had no effect on phosphoglucomutase. These results suggest that the effects of S100A1 and S100B are not nonspecific effects of low molecular weight, acidic proteins. This is the first report of an S100 target protein whose activity is antagonistically regulated by S100A1 and S100B, suggesting that cellular diversity in intracellular calcium signaling pathways may be due, at least in part, to the complement of S100 proteins expressed in different cell types.