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

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Beaulieu, J-M; Gainetdinov, RR; Caron, MG

Published Date

  • April 2007

Published In

Volume / Issue

  • 28 / 4

Start / End Page

  • 166 - 172

PubMed ID

  • 17349698

International Standard Serial Number (ISSN)

  • 0165-6147

Digital Object Identifier (DOI)

  • 10.1016/j.tips.2007.02.006

Language

  • eng

Conference Location

  • England