Abstract
The MPK1 (SLT2) gene of Saccharomyces cerevisiae encodes a mitogen-activated protein kinase that is regulated by a kinase cascade whose known elements are Pkc1 (a homolog of protein kinase C), Bck1 (Slk1) (a homolog of MEK kinase), and the functionally redundant Mpk1 activators Mkk1 and Mkk2 (homologs of MEK). An activated mutation of MKK1, MKK1P386, inhibits growth when overexpressed. This growth-inhibitory effect was suppressed by the mpk1 delta mutation, suggesting that hyperactivation of the Mpk1 pathway is toxic to cells. To search for genes that interact with the Mpk1 pathway, we isolated both chromosomal mutations and dosage suppressor genes that ameliorate the growth-inhibitory effect of overexpressed Mkk1P386. One of the genes identified by the analysis of chromosomal mutations is RLM1 (resistance to lethality of MKK1P386 overexpression), which encodes a protein homologous to a conserved domain of the MADS (Mcm1, Agamous, Deficiens, and serum response factor) box family of transcription factors. Although rlm1 delta cells grow normally at any temperature, they display a caffeine-sensitive phenotype similar to that observed in mutants defective in BCK1, MKK1/MKK2, or MPK1. A gene fusion that provides Rlm1 with a transcriptional activation domain of Gal4 suppresses bck1 delta and mpk1 delta. A screening for dosage suppressors yielded the MSG5 genes, which encode a dual-specificity protein phosphatase. Our results suggest that Rlm1 functions as a transcription factor downstream of Mpk1 that is subject to activation by the Mpk1 mitogen-activated protein kinase pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Caffeine / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cloning, Molecular
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Fungal Proteins / biosynthesis
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Fungal Proteins / physiology*
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Genes, Fungal / genetics
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Genetic Complementation Test
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MADS Domain Proteins
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases*
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Mutation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / physiology*
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Protein Tyrosine Phosphatases / biosynthesis
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Recombinant Fusion Proteins / biosynthesis
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Restriction Mapping
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae Proteins*
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Sequence Deletion
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Sequence Homology, Amino Acid
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Signal Transduction / physiology
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Suppression, Genetic
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Transcription Factors / chemistry
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Transcription Factors / genetics*
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Transcription Factors / physiology
Substances
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Fungal Proteins
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MADS Domain Proteins
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RLM1 protein, S cerevisiae
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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Caffeine
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases
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SLT2 protein, S cerevisiae
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases
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MSG5 protein, S cerevisiae
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Protein Tyrosine Phosphatases
Associated data
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GENBANK/D63340
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GENBANK/U43281