title: Ste5 RING-H2 domain: role in Ste4-promoted oligomerization for yeast pheromone signaling.
abstract: Ste5 is a scaffold for the mitogen-activated protein kinase (MAPK) cascade components in a yeast pheromone response pathway. Ste5 also associates with Ste4, the beta subunit of a heterotrimeric guanine nucleotide-binding protein, potentially linking receptor activation to stimulation of the MAPK cascade. A RING-H2 motif at the Ste5 amino terminus is apparently essential for function because Ste5(C177S) and Ste5(C177A C180A) mutants did not rescue the mating defect of a ste5Delta cell. In vitro Ste5(C177A C180A) bound each component of the MAPK cascade, but not Ste4. Unlike wild-type Ste5, the mutant did not appear to oligomerize; however, when fused to a heterologous dimerization domain (glutathione S-transferase), the chimeric protein restored mating in an ste5Delta cell and an ste4Delta ste5Delta double mutant. Thus, the RING-H2 domain mediates Ste4-Ste5 interaction, which is a prerequisite for Ste5-Ste5 self-association and signaling.
authors.affiliation: Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: C
authors.initials: C
authors.lastname: Inouye
authors.forename: N
authors.initials: N
authors.lastname: Dhillon
authors.forename: J
authors.initials: J
authors.lastname: Thorner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005816:Genetic Complementation Test; D005982:Glutathione Transferase / Q000737:chemistry; D020962:Heterotrimeric GTP-Binding Proteins; D000072235:Mating Factor; D008969:Molecular Sequence Data; D010455:Peptides / Q000502:physiology*; D010675:Pheromones / Q000502:physiology; D017354:Point Mutation; D011108:Polymers; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014170:Transformation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005656:Fungal Proteins; D044387:GTP-Binding Protein beta Subunits; D010455:Peptides; D010675:Pheromones; D011108:Polymers; D011993:Recombinant Fusion Proteins; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C067576:Ste4 protein, S cerevisiae; D000072235:Mating Factor; D005982:Glutathione Transferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins