Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes

摘要: Merozoites of malaria parasites invade red blood cells (RBCs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for pathogenesis. Here, we report a protein kinase-mediated signalling pathway involving host RBC PAK1 MEK1, which do not have orthologues in the Plasmodium kinome, is selectively stimulated falciparum-infected (versus uninfected) RBCs, as determined use phospho-specific antibodies directed against activated forms these enzymes. Pharmacological interference with MEK PAK function using highly specific allosteric inhibitors their known cellular IC50 ranges results parasite death. Furthermore, parasiticidal effects vitro on hepatocyte erythrocyte rodent berghei, indicating conservation this subversive strategy parasites. These findings profound implications novel strategies antimalarial chemotherapy.