A novel protein phosphatase inhibitor, tautomycin. Effect on smooth muscle.
The antibiotic, tautomycin, was found to be a potent inhibitor of protein phosphatases and equally effective for the type-1 and type-2A enzymes. For the catalytic subunits of the type-1 and type-2A phosphatases the IC50 value was 22 to 32 nM. For the phosphatase activity present in chicken gizzard actomyosin the IC50 value was 6 nM. Tautomycin had no effect on myosin light chain kinase activity. Tautomycin induced a Ca(2+)-independent contraction of intact and permeabilized smooth muscle fibers and this was accompanied by an increase in the level of myosin phosphorylation. Thus, tautomycin by virtue of its ability to inhibit phosphatase activity is a valuable addition for studying the role of protein phosphorylation.
Hori
M
M
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
Magae
J
J
Han
Y G
YG
Hartshorne
D J
DJ
Karaki
H
H
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D046911:Macromolecular Substances; D008387:Marine Toxins; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009219:Myosin-Light-Chain Kinase / Q000187:drug effects; D009218:Myosins / Q000378:metabolism; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D010766:Phosphorylation; D011714:Pyrans; D011817:Rabbits; D051381:Rats; D013141:Spiro Compounds; D014700:Verapamil / Q000494:pharmacology
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D046911:Macromolecular Substances; D008387:Marine Toxins; D010080:Oxazoles; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; C059041:calyculin A; D014700:Verapamil; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D009218:Myosins; D002118:Calcium