Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter.
Yeast cells display an adaptive stress response when exposed to weak organic acids at low pH. This adaptation is important in the spoilage of preserved foods, as it allows growth in the presence of weak acid food preservatives. In Saccharomyces cerevisiae, this stress response leads to strong induction of the Pdr12 ATP-binding cassette (ABC) transporter, which catalyses the active efflux of weak acid anions from the cytosol of adapted cells. S. cerevisiae cells lacking the Cmk1 isoform of Ca2+-calmodulin-dependent protein kinase are intrinsically resistant to weak acid stress, in that they do not need to spend a long adaptive period in lag phase before resuming growth after exposure to this stress. This resistance of the cmk1 mutant is Pdr12 dependent and, unlike with wild-type S. cerevisiae, cmk1 cells are capable of performing Pdr12-specific functions such as energy-dependent cellular extrusion of fluorescein and benzoate. However, they have neither higher PDR12 gene promoter activity nor higher Pdr12 protein levels. The increased Pdr12 activity in cmk1 cells is therefore caused by Cmk1 exerting a negative post-transcriptional influence over the activity of the Pdr12 ABC transporter, a transporter protein that is constitutively expressed in low-pH yeast cultures. This is the first preliminary evidence that shows a protein kinase, either directly or indirectly, regulating the activity of a yeast ABC transporter.
Microbiology Department, Unilever Research Colworth, Sharnbrook, Bedford MK44 1LQ, UK.
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Holyoak
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Thompson
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Ortiz Calderon
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Hatzixanthis
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B
Bauer
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Kuchler
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Piper
P J
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Coote
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000143:Acids / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005656:Fungal Proteins; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009930:Organic Chemicals / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000143:Acids; D005656:Fungal Proteins; D009930:Organic Chemicals; D020928:Mitogen-Activated Protein Kinases; C409987:cmk1 protein, Colletotrichum lagenarium