ABSTRACT

I. Introduction Even simple unicellular fungi such as Pneumocystis have evolved sophisticated mechanisms to sense and respond to environmental cues by activating switches that result in coordinated changes in cellular physiology. The ability of the organism to respond is critical to survival within the host environment, for adaptation to host immune responses, and for regulation of life-cycle and cell-cycle events (1). These signaling pathways, in most instances, comprise protein kinases and phosphatases whose activity is regulated by cell surface or intracellular receptor proteins often in conjunction with GTP-binding proteins (Fig. 1) (2). A myriad of additional intracellular proteins interact with the core signaling pathways to regulate and coordinate function. Activated signaling proteins act directly on cellular target proteins modulating protein activity or on transcription factors regulating target protein expression. Although the components and interactions of these signal transduction pathways are well characterized in model yeasts, relatively few components have been identified in Pneumocystis. To date, all characterization of these components has been performed in rat-derived Pneumocystis carinii.