Binder U, Oberparleiter C, Meyer V, Marx F
THE ANTIFUNGAL PROTEIN PAF INTERFERES WITH PKC/MPK AND cAMP/PKA SIGNALING OF ASPERGILLUS NIDULANS. [JOURNAL ARTICLE]
Mol Microbiol 2009 Nov 2.
SUMMARY The Penicillium chrysogenum antifungal protein PAF inhibits polar growth and induces apoptosis in Aspergillus nidulans. We report here that two signaling cascades are implicated in its antifungal activity. PAF activates the cAMP/protein kinase A (Pka) signaling cascade. A pkaA deletion mutant exhibited reduced sensitivity towards PAF. This was substantiated by the use of pharmacological modulators: PAF aggravated the effect of the activator 8-Br-cAMP and partially relieved the repressive activity of caffeine. Furthermore, the Pkc/mitogen-activated protein kinase (Mpk) signaling cascade mediated basal resistance to PAF which was independent of the small GTPase RhoA. Nonfunctional mutations of both genes resulted in hypersensitivity towards PAF. PAF did not increase MpkA phosphorylation or induce enzymes involved in the remodeling of the cell wall, which normally occurs in response to activators of the cell wall integrity pathway. Notably, PAF exposure resulted in actin gene repression and a deregulation of the chitin deposition at hyphal tips of A. nidulans which offers an explanation for the morphological effects evoked by PAF and which could be attributed to the interconnection of the two signaling pathways. Thus, PAF represents an excellent tool to study signaling pathways in this model organism and to define potential fungal targets to develop new antifungals.
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