TY - JOUR
T1 - Serine/Threonine phosphatase activity of calcineurin is inhibited by sodium orthovanadate and dithiothreitol reverses the inhibitory effect
AU - Morioka, Motohiro
AU - Fukunaga, Kohji
AU - Kawano, Takayuki
AU - Hasegawa, Shu
AU - Korematsu, Kohjiro
AU - Kai, Yutaka
AU - Hamada, Jun ichiro
AU - Miyamoto, Eishichi
AU - Ushio, Yukitaka
PY - 1998/12/18
Y1 - 1998/12/18
N2 - 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.
AB - 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.
KW - Calcineurin
KW - Sodium orthovanadate
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U2 - 10.1006/bbrc.1998.9783
DO - 10.1006/bbrc.1998.9783
M3 - Article
C2 - 9878539
AN - SCOPUS:0032545336
VL - 253
SP - 342
EP - 345
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -