title: Serine/threonine phosphatase activity of calcineurin is inhibited by sodium orthovanadate and dithiothreitol reverses the inhibitory effect.
abstract: Orthovanadate is known to be an inhibitor of protein tyrosine phosphatases. However, we found that it inhibited calcineurin which has the activity of a serine/threonine protein phosphatase, using casein phosphorylated by cyclic AMP-dependent protein kinase as a substrate. Orthovanadate inhibits the Mn2+-activated activity of purified calcineurin to 20%; this is not the case without Mn2+. Furthermore, 10 mM dithiothreitol (DTT) reversed the inhibitory effects of orthovanadate. Orthovanadate showed the same inhibitory effect for calcineurin activity in homogenates as for the purified enzyme; the inhibitory effect was reversed by DTT. These results indicate that orthovanadate inhibits not only protein tyrosine phosphatases as reported, but also serine/threonine phosphatase activity of calcineurin.
authors.affiliation: Department of Neurosurgery, Kumamoto University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morioka
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Korematsu
authors.forename: Y
authors.initials: Y
authors.lastname: Kai
authors.forename: J
authors.initials: J
authors.lastname: Hamada
authors.forename: E
authors.initials: E
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ushio
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002417:Cattle; D004229:Dithiothreitol / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D012996:Solutions; D013997:Time Factors; D014638:Vanadates / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D012996:Solutions; D014638:Vanadates; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D004229:Dithiothreitol