Dataset Information

MSI1, a negative regulator of the RAS-cAMP pathway in Saccharomyces cerevisiae.

ABSTRACT: We have previously demonstrated that the IRA1-encoded protein inhibits the function of the RAS protein in a fashion antagonistic to the function of the CDC25 protein in the RAS-cAMP pathway in Saccharomyces cerevisiae. In an attempt to identify genes involved in the regulation of this pathway, high-copy-number plasmid suppressors of the heat shock sensitivity of the ira1 mutation were isolated. One such suppressor, MSI1, was found to encode a putative protein of 422 amino acids that shows homology to the beta subunit of the mammalian guanine nucleotide-binding regulatory proteins. Overexpression of the MSI1 gene could suppress the heat shock sensitivity and the defect in sporulation caused by the ira1 and RAS2Val19 mutations but not those of the bcy1 mutation. Furthermore, the high level of intracellular cAMP in ira1 and RAS2Val19 cells was reduced by the MSI1 gene carried on a YEp-based plasmid. These results suggest that the MSI1 protein is a negative regulator of the RAS-mediated induction of cAMP in S. cerevisiae.

SUBMITTER: Ruggieri R

PROVIDER: S-EPMC298373 | biostudies-other | 1989 Nov

REPOSITORIES: biostudies-other

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MSI1, a negative regulator of the RAS-cAMP pathway in Saccharomyces cerevisiae.

Ruggieri R R Tanaka K K Nakafuku M M Kaziro Y Y Toh-e A A Matsumoto K K

Proceedings of the National Academy of Sciences of the United States of America 19891101 22

We have previously demonstrated that the IRA1-encoded protein inhibits the function of the RAS protein in a fashion antagonistic to the function of the CDC25 protein in the RAS-cAMP pathway in Saccharomyces cerevisiae. In an attempt to identify genes involved in the regulation of this pathway, high-copy-number plasmid suppressors of the heat shock sensitivity of the ira1 mutation were isolated. One such suppressor, MSI1, was found to encode a putative protein of 422 amino acids that shows homolo ...[more]

PMID: 2554329

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Project description:BackgroundCyclic adenosine monophosphate (cAMP) has a key signaling role in all eukaryotic organisms. In Saccharomyces cerevisiae, it is the second messenger in the Ras/PKA pathway which regulates nutrient sensing, stress responses, growth, cell cycle progression, morphogenesis, and cell wall biosynthesis. A stochastic model of the pathway has been reported.ResultsWe have created deterministic mathematical models of the PKA module of the pathway, as well as the complete cAMP pathway. First, a simplified conceptual model was created which reproduced the dynamics of changes in cAMP levels in response to glucose addition in wild-type as well as cAMP phosphodiesterase deletion mutants. This model was used to investigate the role of the regulatory Krh proteins that had not been included previously. The Krh-containing conceptual model reproduced very well the experimental evidence supporting the role of Krh as a direct inhibitor of PKA. These results were used to develop the Complete cAMP Model. Upon simulation it illustrated several important features of the yeast cAMP pathway: Pde1p is more important than is Pde2p for controlling the cAMP levels following glucose pulses; the proportion of active PKA is not directly proportional to the cAMP level, allowing PKA to exert negative feedback; negative feedback mechanisms include activating Pde1p and deactivating Ras2 via phosphorylation of Cdc25. The Complete cAMP model is easier to simulate, and although significantly simpler than the existing stochastic one, it recreates cAMP levels and patterns of changes in cAMP levels observed experimentally in vivo in response to glucose addition in wild-type as well as representative mutant strains such as pde1Delta, pde2Delta, cyr1Delta, and others. The complete model is made available in SBML format.ConclusionWe suggest that the lower number of reactions and parameters makes these models suitable for integrating them with models of metabolism or of the cell cycle in S. cerevisiae. Similar models could be also useful for studies in the human pathogen Candida albicans as well as other less well-characterized fungal species.

Dataset Information

MSI1, a negative regulator of the RAS-cAMP pathway in Saccharomyces cerevisiae.

Publications

MSI1, a negative regulator of the RAS-cAMP pathway in Saccharomyces cerevisiae.

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