期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 85, 期 16, 页码 3505-3514出版社
WILEY
DOI: 10.1002/jnr.21414
关键词
signal transduction; G-protein; GPCR; dominant negative mutations
资金
- NEI NIH HHS [R01 EY 19843, R01 EY012682, R01 EY 12682] Funding Source: Medline
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 G alpha 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 G alpha subunits in which mutations can give rise to a dominant negative phenotype. Such a mutant G alpha would compete with wild-type Got for binding to other proteins involved in the G-protein cycle and either block or reduce the response caused by wild-type G alpha. To date, there are three different mechanisms described for dominant negative G alpha subunits: sequestration of the G beta gamma subunits, sequestration of the activated GPCR by the heterotrimeric complex, and sequestration of the activated GPCR by nucleotide-free G alpha. This review focuses on the development of dominant negative G alpha subunits, the different mechanisms used by various mutant G alpha subunits, and potential structural changes underlying the dominant negative effects. (C) 2007 Wiley-Liss, Inc.
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