期刊
NEUROPHARMACOLOGY
卷 47, 期 -, 页码 14-23出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2004.05.010
关键词
dopamine; serotonin; cocaine; amphetamine; nicotine; opiate; protein; phosphorylation; protein phosphatase
资金
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA010044] Funding Source: NIH RePORTER
- NIDA NIH HHS [P01 DA010044] Funding Source: Medline
The dopamine- and cAMP-regulated phosphoprotein, M, 32 kDa (DARPP-32), plays a key role in dopaminoceptive neurons in the neostriatum (and likely in other brain regions) in signal transduction pathways regulated by a variety of neurotransmitters, neuromodulators, and neuropeptides. Phosphorylation at Thr(34) by protein kinase A converts DARPP-32 into a potent inhibitor of the multifunctional serine/threonine protein phosphatase, PP-1. Phosphorylation at Thr(75) by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state of phosphorylation of DARPP-32 at Thr34 also depends on the phosphorylation state of Ser(102) and Ser(137), which are phosphorylated by CK2 and CK1, respectively. By virtue of its regulation of its four phosphorylation sites by a large number of physiological and pharmacological stimuli, and through its ability to modulate the activity of PP-1 and protein kinase A, DARPP-32 plays a key role in integrating a variety of electrophysiological, transcriptional, and behavioral responses. This review focuses on the critical role that DARPP-32 plays in mediating the actions of a broad range of drugs of abuse. (C) 2004 Elsevier Ltd. All rights reserved.
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