Mechanisms of dominant negative G-protein alpha subunits

Brandy Barren; Nikolai O Artemyev

doi:10.1002/jnr.21414

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Mechanisms of dominant negative G-protein alpha subunits

Journal article

Peer reviewed

Mechanisms of dominant negative G-protein alpha subunits

Brandy Barren and Nikolai O Artemyev

Journal of neuroscience research, Vol.85(16), pp.3505-3514

12/2007

DOI: 10.1002/jnr.21414

PMID: 17639598

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Abstract

G-protein-coupled receptors (GPCRs) represent the largest class of membrane proteins and are the targets of 25-50% of drugs currently on the market. Dominant negative mutant Galpha subunits of heterotrimeric G-proteins have been extensively utilized to delineate G-protein signaling pathways and represent a promising new tool to study GPCR-dependent signaling in the CNS. There are different regions in various types of Galpha subunits in which mutations can give rise to a dominant negative phenotype. Such a mutant Galpha would compete with wild-type Galpha for binding to other proteins involved in the G-protein cycle and either block or reduce the response caused by wild-type Galpha. To date, there are three different mechanisms described for dominant negative Galpha subunits: sequestration of the Gbetagamma subunits, sequestration of the activated GPCR by the heterotrimeric complex, and sequestration of the activated GPCR by nucleotide-free Galpha. This review focuses on the development of dominant negative Galpha subunits, the different mechanisms used by various mutant Galpha subunits, and potential structural changes underlying the dominant negative effects.

Guanine Nucleotide Exchange Factors - genetics

Animals

Humans

GTP-Binding Protein gamma Subunits - genetics

GTP-Binding Protein alpha Subunits - genetics

Receptors, G-Protein-Coupled - genetics

Signal Transduction - genetics

Mutation - genetics

GTP-Binding Protein beta Subunits - genetics

Protein Subunits - genetics

Details

Title: Subtitle: Mechanisms of dominant negative G-protein alpha subunits
Creators: Brandy Barren - Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, 51 Newton Road, Iowa City, IA 52242, USA
Nikolai O Artemyev
Resource Type: Journal article
Publication Details: Journal of neuroscience research, Vol.85(16), pp.3505-3514
DOI: 10.1002/jnr.21414
PMID: 17639598
NLM abbreviation: J Neurosci Res
ISSN: 0360-4012
eISSN: 1097-4547
Publisher: United States
Grant note: R01 EY 12682 / NEI NIH HHS R01 EY 19843 / NEI NIH HHS R01 EY012682 / NEI NIH HHS
Language: English
Date published: 12/2007
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984065478702771

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