Mutation of RGA1, which encodes a putative GTPase-activating protein for the polarity-establishment protein Cdc42p, activates the pheromone-response pathway in the yeast Saccharomyces cerevisiae

We have selected yeast mutants that exhibit a constitutively active pheromone-response pathway in the absence of the beta subunit of the trimeric G protein. Genetic analysis of one such mutant revealed that it contained recessive mutations in two distinct genes, both of which contributed to the cons...

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Bibliographic Details
Published in:Genes & development 1995-12, Vol.9 (23), p.2949-2963
Main Authors: Stevenson, B J, Ferguson, B, De Virgilio, C, Bi, E, Pringle, J R, Ammerer, G, Sprague, Jr, G F
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
beta-Galactosidase - genetics
cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Cell Cycle Proteins - metabolism
Cell Polarity - genetics
Drosophila Proteins
Gene Expression Regulation, Fungal
GTP-Binding Proteins - biosynthesis
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
GTPase-Activating Proteins
Insect Proteins
Molecular Sequence Data
Mutation
Osmolar Concentration
Pheromones - genetics
Pheromones - metabolism
Protein Kinases
Proteins - chemistry
Proteins - genetics
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Sequence Homology, Amino Acid
Signal Transduction
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Summary:We have selected yeast mutants that exhibit a constitutively active pheromone-response pathway in the absence of the beta subunit of the trimeric G protein. Genetic analysis of one such mutant revealed that it contained recessive mutations in two distinct genes, both of which contributed to the constitutive phenotype. One mutation identifies the RGA1 locus (Rho GTPase activating protein), which encodes a protein with homology to GAP domains and to LIM domains. Deletion of RGA1 is sufficient to activate the pathway in strains lacking the G beta subunit. Moreover, in wild-type strains, deletion of RGA1 increases signaling in the pheromone pathway, whereas over-expression of RGA1 dampens signaling, demonstrating that Rga1p functions as a negative regulator of the pheromone response pathway. The second mutation present in the original mutant proved to be an allele of a known gene, PBS2, which encodes a putative protein kinase that functions in the high osmolarity stress pathway. The pbs2 mutation enhanced the rga1 mutant phenotype, but by itself did not activate the pheromone pathway. Genetic and two-hybrid analyses indicate that an important target of Rga1p is Cdc42p, a p21 GTPase required for polarity establishment and bud emergence. This finding coupled with recent experiments with mammalian and yeast cells indicating that Cdc42p can interact with and activate Ste20p, a protein kinase that operates in the pheromone pathway, leads us to suggest that Rga1p controls the activity of Cdc42p, which in turn controls the magnitude of signaling in the pheromone pathway via Ste20p.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.9.23.2949