Protein kinase C-like 1 (Pkc1)

Protein kinase C-like 1 (Pkc1) is a critical serine/threonine kinase in fungi, such as Saccharomyces cerevisiae and Candida albicans, where it functions as the primary regulator of the cell wall integrity (CWI) signaling pathway (Levin, 2005, Microbiol Mol Biol Rev). It is activated by the small GTPase Rho1 and subsequently triggers a downstream mitogen-activated protein kinase (MAPK) cascade involving Bck1, Mkk1/2, and Slt2/Mpk1 (UniProt P24583). This pathway is essential for maintaining the fungal cell wall during growth, morphogenesis, and environmental stress. Because Pkc1 is indispensable for fungal survival and possesses structural features distinct from human protein kinase C (PKC) isoforms, it is a highly attractive target for antifungal therapy (Sussman et al., 2004, Eukaryot Cell). Inhibition of Pkc1 results in cell wall weakening, osmotic fragility, and cell death. Compounds like cercosporamide have been identified as selective inhibitors of Pkc1, showing efficacy against various pathogenic fungi (PubMed: 15507491). Therapeutic challenges include achieving high selectivity over human PKC isoforms to minimize systemic toxicity, while research continues to explore Pkc1 inhibitors as a means to combat drug-resistant fungal infections.

Other names

PKC1STT1Cell wall integrity kinaseSerine/threonine-protein kinase PKC1

Inhibition of the cell wall integrity (CWI) signaling pathway, leading to defective cell wall synthesis and osmotic lysis of fungal cells.