Title

Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor

UMMS Affiliation

Program in Systems Biology

Date

2-12-2008

Document Type

Article

Medical Subject Headings

Adenosine Triphosphatases; GTP-Binding Proteins; Gene Expression Regulation, Fungal; Guanine Nucleotide Exchange Factors; Pheromones; Receptors, Cell Surface; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Time Factors

Disciplines

Biochemistry

Abstract

G protein-coupled receptors (GPCRs) mediate responses to a broad range of chemical and environmental signals. In yeast, a pheromone-binding GPCR triggers events leading to the fusion of haploid cells. In general, GPCRs function as guanine-nucleotide exchange factors (GEFs); upon agonist binding, the receptor induces a conformational change in the G protein alpha subunit, resulting in exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and in signal initiation. Signaling is terminated when GTP is hydrolyzed to GDP [1]. This well-established paradigm has in recent years been revised to include new components that rates of GDP release, GTP binding [2-8], and GTP hydrolysis[9, 10]. Here we report the discovery of a nonreceptor GEF, Arr4. Like receptors, Arr4 binds directly to the G protein,accelerates guanine-nucleotide exchange, and stabilizes the nucleotide-free state of the a subunit. Moreover, Arr4 promotes G protein-dependent cellular responses, including mitogen-activated protein kinase (MAPK) phosphorylation,new-gene transcription, and mating. In contrast to knownGPCRs, however, Arr4 is not a transmembrane receptor,but rather a soluble intracellular protein. Our data suggest that intracellular proteins function in cooperation with mating pheromones to amplify G protein signaling, thereby leading to full pathway activation.

Rights and Permissions

Citation: Lee MJ, Dohlman HG. Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor. Curr Biol. 2008 Feb 12;18(3):211-5. doi: 10.1016/j.cub.2008.01.007. Link to article on publisher's site

Comments

At the time of publication, Michael J. Lee was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

Journal Title

Current biology : CB

PubMed ID

18261907