Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca2+-calmodulin-dependent protein kinase

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Published inMolecular and Cellular Biology Vol. 16; no. 9; pp. 4824 - 4831
Main Authors Moser, Michael J., Geiser, John R., Davis, Trisha N.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.09.1996
Taylor & Francis
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The cmd1-6 allele contains three mutations that block Ca 2+ binding to calmodulin from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose viability during cell cycle arrest induced by the mating pheromone α-factor. The 50% lethal dose (LD 50 )of α-factor for the calmodulin mutant is almost fivefold below the LD 50 for a wild-type strain. The calmodulin mutants are not more sensitive to α-factor, as measured by activation of a pheromone-responsive reporter gene. Two observations indicate that activation of the Ca 2+ -calmodulin-dependent protein phosphatase calcineurin contributes to survival of pheromone-induced arrest. First, deletion of the gene encoding the calcineurin regulatory B subunit, CNB1, from a wild-type strain decreases the LD 50 of α-factor but has no further effect on a cmd1-6 strain. Second, a dominant constitutive calcineurin mutant partially restores the ability of the cmd1-6 strain to survive exposure to α-factor. Activation of the Ca 2+ -calmodulin-dependent protein kinase (CaMK) also contributes to survival, thus revealing a new function for this enzyme. Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD 50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain. Furthermore, the LD 50 of α-factor for a mutant in which the calcineurin and CaMK genes have been deleted is the same as that for the calmodulin mutant. Finally, the CaMK and calcineurin pathways appear to be independent since the ability of constitutive calcineurin to rescue a cmd1-6 strain is not blocked by deletion of the CaMK genes.
The cmd1-6 allele contains three mutations that block Ca2+ binding to calmodulin from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose viability during cell cycle arrest induced by the mating pheromone alpha-factor. The 50% lethal dose (LD50) of alpha-factor for the calmodulin mutant is almost fivefold below the LD50 for a wild-type strain. The calmodulin mutants are not more sensitive to alpha-factor, as measured by activation of a pheromone-responsive reporter gene. Two observations indicate that activation of the Ca2+-calmodulin-dependent protein phosphatase calcineurin contributes to survival of pheromone-induced arrest. First, deletion of the gene encoding the calcineurin regulatory B subunit, CNB1, from a wild-type strain decreases the LD50 of alpha-factor but has no further effect on a cmd1-6 strain. Second, a dominant constitutive calcineurin mutant partially restores the ability of the cmd1-6 strain to survive exposure to alpha-factor. Activation of the Ca2+-calmodulin-dependent protein kinase (CaMK) also contributes to survival, thus revealing a new function for this enzyme. Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain. Furthermore, the LD50 of alpha-factor for a mutant in which the calcineurin and CaMK genes have been deleted is the same as that for the calmodulin mutant. Finally, the CaMK and calcineurin pathways appear to be independent since the ability of constitutive calcineurin to rescue a cmd1-6 strain is not blocked by deletion of the CaMK genes.
Author J R Geiser
M J Moser
T N Davis
AuthorAffiliation Department of Biochemistry, University of Washington, Seattle 98195, USA
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The cmd1-6 allele contains three mutations that block Ca 2+ binding to calmodulin from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose...
The cmd1-6 allele contains three mutations that block Ca2+ binding to calmodulin from Saccharomyces cerevisiae. We find that strains containing cmd1-6 lose...
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SubjectTerms Base Sequence
Calcineurin
Calcium - physiology
Calcium-Calmodulin-Dependent Protein Kinases - genetics
Calcium-Calmodulin-Dependent Protein Kinases - physiology
Calmodulin - genetics
Calmodulin - physiology
Calmodulin-Binding Proteins - physiology
Enzyme Activation
Fungal Proteins - physiology
Mating Factor
Molecular Sequence Data
Peptides - physiology
Phosphoprotein Phosphatases - physiology
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - physiology
Sequence Deletion
Title Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca2+-calmodulin-dependent protein kinase
URI http://mcb.asm.org/content/16/9/4824.abstract
https://www.tandfonline.com/doi/abs/10.1128/MCB.16.9.4824
https://www.ncbi.nlm.nih.gov/pubmed/8756641
https://pubmed.ncbi.nlm.nih.gov/PMC231484
Volume 16
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