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Titolo:
Role of calcineurin and protein phosphatase-2A in the regulation of DARPP-32 dephosphorylation in neostriatal neurons
Autore:
Nishi, A; Snyder, GL; Nairn, AC; Greengard, P;
Indirizzi:
Kurume Univ, Sch Med, Dept Physiol, Fukuoka 8300011, Japan Kurume Univ Fukuoka Japan 8300011 , Dept Physiol, Fukuoka 8300011, Japan Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA Rockefeller Univ New York NY USA 10021 urosci Lab, New York, NY 10021 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 72, anno: 1999,
pagine: 2015 - 2021
SICI:
0022-3042(199905)72:5<2015:ROCAPP>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOSINE 3'-5'-MONOPHOSPHATE-REGULATED PHOSPHOPROTEIN; STRIATONIGRAL NEURONS; OKADAIC ACID; CALYCULIN-A; RAT-BRAIN; IN-VITRO; DOPAMINE; PHOSPHORYLATION; INHIBITOR-1; ACTIVATION;
Keywords:
cyclic AMP-dependent protein kinase; cyclosporin A; dopamine; okadaic acid; protein phosphatase-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Nishi, A Kurume Univ, Sch Med, Dept Physiol, 67 Asahi Machi, Fukuoka 8300011, Japan Kurume Univ 67 Asahi Machi Fukuoka Japan 8300011 8300011, Japan
Citazione:
A. Nishi et al., "Role of calcineurin and protein phosphatase-2A in the regulation of DARPP-32 dephosphorylation in neostriatal neurons", J NEUROCHEM, 72(5), 1999, pp. 2015-2021

Abstract

DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein of M-r 32 kDa, is phosphorylated on Thr(34) by cyclic AMP-dependent protein kinase, resulting in its conversion to a potent inhibitor of protein phosphatase-1 (PP-1), Conversely, Thr(34)-phosphorylated DARPP-32 is dephosphorylated and inactivated in vitro by calcineurin and protein phosphatase-2A (PP-2A). We have investigated the relative contributions of these protein phosphatases tothe regulation of DARPP-32 dephosphorylation in mouse neostriatal slices. Cyclosporin A (5 mu M), a calcineurin inhibitor, maximally increased the level of phosphorylated DARPP-32 by 17 +/- 2-fold. Okadaic acid (1 mu M), an inhibitor of PP-1 and PP-2A, had a smaller effect, increasing phospho-DARPP-32 by 5.1 +/- 1.3-fold. The effect of okadaic acid on DARPP-32 phosphorylation was shown to be due to inhibition of PP-2A activity. Incubation of slices in the presence of cyclosporin A plus either okadaic acid or calyculin A, another PP-1/PP-2A inhibitor, caused a synergistic increase in the levelof phosphorylated DARPP-32. The use of Ca2+-free/EGTA medium mimicked the effects of cyclosporin A on DARPP-32 phosphorylation, supporting the conclusion that the action of cyclosporin on DARPP-32 phosphorylation was attributable to blockade of the Ca2+-dependent activation of calcineurin. The results indicate that calcineurin and PP-2A, but not PP-1, act synergistically to maintain a low level of phosphorylated DARPP-32 in neostriatal slices.

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Documento generato il 04/04/20 alle ore 15:11:11