Details

Autor(en) / Beteiligte

• Fox, Deborah S

Titel

Signal transduction in the opportunistic fungal pathogen Pneumocystis carinii: Characterization of a mitogen -activated protein kinase involved in cell integrity

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1999

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Signal transduction pathways are important in the adaptive response of microbes to their environment. A Pneumocystis carinii mitogen-activated protein kinase (MAPK) homologue, Mkp1, has been isolated by sequence similarity screening of P. carinii genomic DNA. 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, Mkc1p of Candida albicans and Mps1p 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 slt2Δ defect fully restored the normal growth rate and partially reduced lysis at elevated temperatures. Complementation of the slt2Δ 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 exposure of P. carinii to conditions of oxidative stress. The preservation of cell wall structure and integrity is important in all aspects of the yeast life cycle, including growth, mating and stress response. It has been proposed that the cell integrity cascade, which includes a PKC (protein kinase C)-activated MAP kinase module, functions as a salvage pathway in response to environmental factors that weaken the fungal cell wall. Rlm1p, a MADS-box transcription factor, has been demonstrated to be a direct target of Slt2p, the MAP kinase of the cell integrity pathway of S. cerevisiae. Mkp1 displays an unusual feature in that it contains a phosphorylation motif repeat (TEYMTEY) within the activation loop not present in any other fungal MAPK identified to date. Mutagenesis of the T186,Y188 phosphorylation motif within the activation domain of Mkp1 results in the loss of detectable kinase activity but still retains partial complementation function. (Abstract shortened by UMI.)