ArticleMolecular and cellular biology1996
Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit).
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 334 citations in OpenAlex.
- Identification and Classification of Fungal GPCR Gene Families.Journal of fungi (Basel, Switzerland) · 2025Article
- A yeast mating platform for multiplex screening of fungal GPCR-ligand interactions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Septin organization is regulated by the Gpa1 ubiquitination domain and endocytic machinery during the yeast pheromone response.Molecular biology of the cell · 2025Article
- A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds.International journal of molecular sciences · 2024Article
- Heterotrimeric G protein signaling without GPCRs: The Gα-binding-and-activating (GBA) motif.The Journal of biological chemistry · 2024Review
- Design patterns of biological cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Class VI G protein-coupled receptors in Aspergillus oryzae regulate sclerotia formation through GTPase-activating activity.Applied microbiology and biotechnology · 2024Article
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Global quantitative understanding of non-equilibrium cell fate decision-making in response to pheromone.iScience · 2023Article
- RGS proteins and their roles in cancer: friend or foe?Cancer cell international · 2023Review
- Cardiac RGS Proteins in Human Heart Failure and Atrial Fibrillation: Focus on RGS4.International journal of molecular sciences · 2023Review
- Coupling Cell Communication and Optogenetics: Implementation of a Light-Inducible Intercellular System in Yeast.ACS synthetic biology · 2023Article
- The Potential Role of R4 Regulators of G Protein Signaling (RGS) Proteins in Type 2 Diabetes Mellitus.Cells · 2022Review
- Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis.Life science alliance · 2022Article
- Mechanism of commitment to a mating partner inMolecular biology of the cell · 2022Article
- Phylogeny of Regulators of G-Protein Signaling Genes inMicroorganisms · 2022Article
- cAMP Signalling Pathway in Biocontrol Fungi.Current issues in molecular biology · 2022Review
- Article
- Endosomal cargo recycling mediated by Gpa1 and phosphatidylinositol 3-kinase is inhibited by glucose starvation.Molecular biology of the cell · 2022Article
- Functions of regulators of G protein signaling 16 in immunity, inflammation, and other diseases.Frontiers in molecular biosciences · 2022Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Sst2 is the prototype for the newly recognized RGS (for regulators of G-protein signaling) family. Cells lacking the pheromone-inducible SST2 gene product fail to resume growth after exposure to pheromone. Conversely, overproduction of Sst2 markedly enhanced the rate of recovery from pheromone-induced arrest in the long-term halo bioassay and detectably dampened signaling in a short-term assay of pheromone response (phosphorylation of Ste4, Gbeta subunit). When the GPA1 gene product (Galpha subunit) is absent, the pheromone response pathway is constitutively active and, consequently, growth ceases. Despite sustained induction of Sst2 (observed with specific anti-Sst2 antibodies), gpa1delta mutants remain growth arrested, indicating that the action of Sst2 requires the presence of Gpa1. The N-terminal domain (residues 3 to 307) of Sst2 (698 residues) has sequence similarity to the catalytic regions of bovine GTPase-activating protein and human neurofibromatosis tumor suppressor protein; segments in the C-terminal domain of Sst2 (between residues 417 and 685) are homologous to other RGS proteins. Both the N- and C-terminal domains were required for Sst2 function in vivo. Consistent with a role for Sst2 in binding to and affecting the activity of Gpa1, the majority of Sst2 was membrane associated and colocalized with Gpa1 at the plasma membrane, as judged by sucrose density gradient fractionation. Moreover, from cell extracts, Sst2 could be isolated in a complex with Gpa1 (expressed as a glutathione S-transferase fusion); this association withstood the detergent and salt conditions required for extraction of these proteins from cell membranes. Also, SST2+ cells expressing a GTPase-defective GPA1 mutant displayed an increased sensitivity to pheromone, whereas sst2 cells did not. These results demonstrate that Sst2 and Gpa1 interact physically and suggest that Sst2 is a direct negative regulator of Gpa1.
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