The Akt-GSK-3 signaling cascade in the actions of doparnine

被引:349
作者
Beaulieu, Jean-Martin [1 ]
Gainetdinov, Raul R. [1 ]
Caron, Marc G. [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
关键词
D O I
10.1016/j.tips.2007.02.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Ca2+ 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.
引用
收藏
页码:166 / 172
页数:7
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