Tautomycin from the bacterium Streptomyces verticillatus: another potent and specific inhibitor of protein phosphatases 1 and 2A

Tautomycin inhibited the catalytic subunits of protein phosphatase-1 (K(i)(app)=0.16 nM) more potently than protein phosphatase 2A (K(i)(app)=0.4 nM), and the native forms of these enzymes in mammalian, protozoan and plant extracts were inhibited in a similar manner. Protein phosphatase 2B was inhibited 10000-fold less potently, while two other phosphatases and six protein kinases were unaffected at 10 mu-M. Okadaic acid prevented the binding of tautomycin to protein phosphatase 2A, indicating a common binding site for both inhibitors. The different relative potencies of tautomycin and okadaic acid for protein phosphatases 1 and 2A suggest that parallel use of both inhibitors may help to identify physiological substrates for each enzyme.