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

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.
Mesh Terms:
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
Curr. Biol.
Date: Feb. 12, 2008
Download Curated Data For This Publication
75249
Switch View:
  • Interactions 9