FIG 11.

Proposed regulatory mechanism of protein tyrosine phosphatases in C. neoformans. Both PTP1 and PTP2 were strongly induced in response to environmental stresses in a Hog1-dependent manner, partly through the Atf1 transcription factor. Ptp1 and Ptp2 localized to both the cytoplasm and the nucleus, with greater enrichment in the nucleus. Both PTPs appeared to have a Hog1-anchoring function. Ptp2 was a major negative-feedback regulator of Hog1 and controlled stress responses, virulence factor productions (melanin, capsule, and urease), and sexual differentiation. However, Ptp2 may also be involved in other signaling pathways, which controlled susceptibilities to heavy metal, flucytosine, and H₂O₂. In contrast, Ptp1 played minor roles in the HOG pathway and also controlled the filamentation process during mating of C. neoformans in a Hog1-independent manner.