Mitogen-activated protein kinase Mkp1 of Pneumocystis carinii complements the slt2Delta defect in the cell integrity pathway of Saccharomyces cerevisiae.
Signal transduction pathways are important in the adaptive response of microbes to their environment. A Pneumocystis carinii extracellular signal-regulated protein kinase (MAPK) homologue, Mkp1, has been isolated by sequence similarity screening of P. carinii genomic DNA. The Mkp1 of P. carinii shows closest homology to other fungal MAP kinases involved in cell integrity signal transduction cascades, including Slt2p/Mpk1p of Saccharomyces cerevisiae, Mkc1 of Candida albicans and Mps1 of Magnaporthe grisea. Defects of Slt2p in S. cerevisiae result in phenotypes of slow growth, and temperature sensitivity in the absence of an osmostabilizer. Overexpression of mkp1 in a strain with the slt2Delta defect fully restored the normal growth rate, and partially reduced lysis at elevated temperatures. Complementation of the slt2Delta defect by Mkp1 demonstrates that Mkp1 is a functional MAP kinase, and that it may be the MAP kinase component of a similar signal transduction cascade within P. carinii. Furthermore, Mkp1 is activated in vitro upon the exposure of P. carinii to conditions of oxidative stress. The investigation of a MAP kinase signal transduction pathway of P. carinii will result in both a better understanding of the mechanism the organism utilizes to respond to environmental changes, and a system to assay responses to these changes.
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Department of Pathology; Infectious Disease Division, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, OH, USA.
Smulian
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AG
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D011010:Pneumocystis / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D011020:Pneumonia, Pneumocystis / Q000382:microbiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D015398:Signal Transduction; D013696:Temperature; D014170:Transformation, Genetic
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae