Tautomycin from the bacterium Streptomyces verticillatus

Abstract

Tautomycin inhibited the catalytic subunits of protein phosphatase-1 (4 = 0.16 nM) more potently than protein phosphatase 2A (K, = 0.4 nM), and the native forms of these enzymes in mammalian, protozoan and $mt extracts were inhibited in a similar manner. Protein phziphatase 2B was inhibited IOOOO-fold less potently, while two other phosphatases and six protein kinases were unaffected at 10 PM. 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.

Protein phosphatase 1 positively regulates stomatal opening in response to blue light in Vicia faba

“…PP1 is most likely to mediate signaling between phototropin and the plasma membrane H ϩ -ATPase (15). To test this, we used tautomycin, a membrane-permeable inhibitor of PP1, which is used frequently to investigate the role of PP1 in various cellular events; because it inhibits PP2A with 10-fold lower sensitivity in vitro (25)(26)(27)(28), it can help to distinguish between responses mediated by the two classes of enzymes. We expected that blue light-dependent H ϩ pumping and stomatal opening were inhibited by this reagent.…”

Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

“…Therefore, the observed effects of CspA or ascomycin could reflect a decrease in the calcineurin-mediated activation of PP1. To examine this possibility, we used the highly specific and potent PP1 inhibitor tautomycin (21), and applied it internally via the pipette to ensure that this inhibitor had ready access to the cytosol. Using this approach, inclusion of 0.1 M tautomycin in the pipette failed to affect the magnitude of the ARC current density measured at Ϫ80 mV with 400 nM internal Ca 2ϩ (0.16 Ϯ 0.03 pA/pF versus 0.19 Ϯ 0.02 pA/pF, n ϭ 5) (Fig.…”

The cyanobacterial toxin microcystin binds covalently to cysteine‐273 on protein phosphatase 1

“…These protein phosphatases are inhibited potently and specifically by a chemically diverse group of naturally occurring toxins that include okadaic acid, a polyketide produced by marine dinoflagellates and the major cause of diarrhetic shellfish poisoning [4); tautomycin. a structurally related polyketide produced by the soil bacterium Streptomyces [5); calyculin A, a phosphorylated poIyketide isolated from the sea sponge Discodermia calyx [6); cantharidin. a simple terpenoid produced as a defence compound by meloid blister beetles [7).…”

“…kinetic analyses [5,8) and competition binding studies [7.10.11) suggest that they, and the specific heat stable protein inhibitors of PPI (inhibitor-I and inhibitor-2 [8)). may share common binding sites on protein serinelthreonine phosphatases.…”