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DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1.

Authors :
Hemmings HC Jr
Greengard P
Tung HY
Cohen P
Source :
Nature [Nature] 1984 Aug 9-15; Vol. 310 (5977), pp. 503-5.
Publication Year :
1984

Abstract

The neurotransmitter dopamine has been demonstrated by biochemical, histochemical and immunocytochemical techniques to be unevenly distributed in the mammalian central nervous system. DARPP-32 (dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32,000) is a neuronal phosphoprotein that displays a regional distribution in the mammalian brain very similar to that of dopamine-containing nerve terminals, being highly concentrated in the basal ganglia. The state of phosphorylation of DARPP-32 can be regulated by dopamine and by cyclic AMP in intact nerve cells, suggesting a role for this phosphoprotein in mediating certain of the effects of dopamine on dopaminoceptive cells. The observation that many of the physical and chemical properties of purified DARPP-32 resemble those of phosphatase inhibitor-1 (inhibitor-1), a widely distributed inhibitor of protein phosphatase-1, suggests that DARPP-32 might also function as a phosphatase inhibitor. We report here that DARPP-32 inhibits protein phosphatase-1 at nanomolar concentrations. Moreover, like inhibitor-1, DARPP-32 is effective as an inhibitor in its phosphorylated but not its dephosphorylated form. Thus, the basal ganglia of mammalian brain contain a region-specific neuronal phosphoprotein that is a protein phosphatase inhibitor.

Details

Language :
English
ISSN :
0028-0836
Volume :
310
Issue :
5977
Database :
MEDLINE
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
6087160
Full Text :
https://doi.org/10.1038/310503a0