Complementation and characterization of the Pneumocystis carinii MAPK, PCM.

Mitogen-activated protein kinase (MAPK) pathways transfer environmental signals into intracellular events such as proliferation and differentiation. Fungi utilize a specific pheromone-induced MAPK pathway to regulate conjugation, formation of an ascus, and entry into meiosis. We have previously identified a MAPK, PCM, from the fungal opportunist Pneumocystis, responsible for causing severe pneumonia in patients with AIDS.

Pneumocystis carinii STE11, an HMG-box protein, is phosphorylated by the mitogen activated protein kinase PCM.

A pheromone-induced mitogen activated protein kinase (MAPK) pathway controls mating in fungi by regulating gene transcription. In the opportunistic fungus Pneumocystis carinii, we have identified a protein containing a high-mobility group (HMG) motif which is homologous to the transcriptional activators STE11 of Schizosaccharomyces pombe and STE12 of Saccharomyces cerevisiae. In fungi, this transcriptional activator functions in sexual development, filamentous growth, and pathogenicity.

Pneumocystis carinii BCK1 functions in a mitogen-activated protein kinase cascade regulating fungal cell-wall assembly.

Pneumocystis pneumonia remains the most common AIDS-defining opportunistic infection in people with HIV. The process by which Pneumocystis carinii constructs its cell wall is not well known, although recent studies reveal that molecules such as beta-1-3-glucan synthetase (GSC1) and environmental pH-responsive genes such as PHR1 are important for cell-wall integrity. In closely related fungi, a specific mitogen-activated protein kinase (MAPK) cascade regulates cell-wall assembly in response to elevated temperature.

Characterization of a lanosterol 14 alpha-demethylase from Pneumocystis carinii.

Pneumocystis carinii (PC) causes severe pneumonia in immunocompromised patients. PC is intrinsically resistant to treatment with azole antifungal medications. The enzyme lanosterol 14 alpha-demethylase (Erg11) is the target for azole antifungals.