Mutations in the SHR5 gene of Saccharomyces cerevisiae suppress Ras function and block membrane attachment and palmitoylation of Ras proteins

V. Jung, L. Chen, S. L. Hofmann, M. Wigler, S. Powers

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We have identified a gene, SHR5, in a screen for extragenic suppressors of the hyperactive RAS2(Val-19) mutation in the budding yeast Saccharomyces cerevisiae. SHR5 was cloned, sequenced, and found to encode a 23-kDa protein not significantly homologous to other proteins in the current data bases. Genetic evidence arguing that Shr5 operates at the level of Ras is presented. We tested whether SHR5, like previously isolated suppressors of hyperactivated RAS2, acts by affecting the membrane attachment and/or posttranslational modification of Ras proteins. We found that less Ras protein is attached to the membrane in shr5 mutants than in wild-type cells and that the Ras proteins are markedly underpalmitoylated, suggesting that Shr5 is involved in palmitoylation of Ras proteins. However, shr5(null) mutants exhibit normal palmitoyltransferase activity measured in vitro. Further, shr5(null) mutations attenuate Ras function in cells containing mutant Ras2 proteins that are not palmitoylated or farnesylated. We conclude that SHR5 encodes a protein that participates in the membrane localization of Ras but also interacts in vivo with completely unprocessed and cytosolic Ras proteins.

Original languageEnglish (US)
Pages (from-to)1333-1342
Number of pages10
JournalMolecular and Cellular Biology
Volume15
Issue number3
StatePublished - 1995

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Lipoylation
ras Proteins
Saccharomyces cerevisiae
Mutation
Membranes
Genes
Proteins
Saccharomycetales
Mutant Proteins
Post Translational Protein Processing
Databases

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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Mutations in the SHR5 gene of Saccharomyces cerevisiae suppress Ras function and block membrane attachment and palmitoylation of Ras proteins. / Jung, V.; Chen, L.; Hofmann, S. L.; Wigler, M.; Powers, S.

In: Molecular and Cellular Biology, Vol. 15, No. 3, 1995, p. 1333-1342.

Research output: Contribution to journalArticle

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AU - Jung, V.

AU - Chen, L.

AU - Hofmann, S. L.

AU - Wigler, M.

AU - Powers, S.

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N2 - We have identified a gene, SHR5, in a screen for extragenic suppressors of the hyperactive RAS2(Val-19) mutation in the budding yeast Saccharomyces cerevisiae. SHR5 was cloned, sequenced, and found to encode a 23-kDa protein not significantly homologous to other proteins in the current data bases. Genetic evidence arguing that Shr5 operates at the level of Ras is presented. We tested whether SHR5, like previously isolated suppressors of hyperactivated RAS2, acts by affecting the membrane attachment and/or posttranslational modification of Ras proteins. We found that less Ras protein is attached to the membrane in shr5 mutants than in wild-type cells and that the Ras proteins are markedly underpalmitoylated, suggesting that Shr5 is involved in palmitoylation of Ras proteins. However, shr5(null) mutants exhibit normal palmitoyltransferase activity measured in vitro. Further, shr5(null) mutations attenuate Ras function in cells containing mutant Ras2 proteins that are not palmitoylated or farnesylated. We conclude that SHR5 encodes a protein that participates in the membrane localization of Ras but also interacts in vivo with completely unprocessed and cytosolic Ras proteins.

AB - We have identified a gene, SHR5, in a screen for extragenic suppressors of the hyperactive RAS2(Val-19) mutation in the budding yeast Saccharomyces cerevisiae. SHR5 was cloned, sequenced, and found to encode a 23-kDa protein not significantly homologous to other proteins in the current data bases. Genetic evidence arguing that Shr5 operates at the level of Ras is presented. We tested whether SHR5, like previously isolated suppressors of hyperactivated RAS2, acts by affecting the membrane attachment and/or posttranslational modification of Ras proteins. We found that less Ras protein is attached to the membrane in shr5 mutants than in wild-type cells and that the Ras proteins are markedly underpalmitoylated, suggesting that Shr5 is involved in palmitoylation of Ras proteins. However, shr5(null) mutants exhibit normal palmitoyltransferase activity measured in vitro. Further, shr5(null) mutations attenuate Ras function in cells containing mutant Ras2 proteins that are not palmitoylated or farnesylated. We conclude that SHR5 encodes a protein that participates in the membrane localization of Ras but also interacts in vivo with completely unprocessed and cytosolic Ras proteins.

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