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

UMMS Affiliation

Program in Systems Biology

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Document Type



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




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.

DOI of Published Version



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

Journal/Book/Conference Title

Current biology : CB


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

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