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Trends Pharmacol Sci. 2007 Apr;28(4):166-72. Epub 2007 Mar 8.

The Akt-GSK-3 signaling cascade in the actions of dopamine.

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1
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. m.caron@cellbio.duke.edu

Abstract

Drugs that act on dopamine neurotransmission are important tools for the management of multiple neuropsychiatric disorders. Classically, dopamine receptors have been shown to regulate cAMP-PKA (protein kinase A) and Ca(2+) pathways through G-protein-mediated signaling. However, it has become apparent that, in addition to this canonical action, D(2)-class dopamine receptors can function through a protein kinase B (Akt)-GSK-3 (glycogen synthase kinase 3) signaling cascade. This novel signaling mode involves the multifunctional scaffolding protein beta-arrestin 2, which has a role in G-protein-coupled receptor (GPCR) desensitization. In this article, we provide an overview of how this dual function of components of the GPCR desensitization machinery relates to dopamine-receptor-mediated responses and we summarize recent insights into the relevance of the Akt-GSK-3 signaling cascade for the expression of dopamine-associated behaviors and the actions of dopaminergic drugs.

PMID:
17349698
DOI:
10.1016/j.tips.2007.02.006
[Indexed for MEDLINE]
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