Staurosporine inhibits invasion of erythrocytes by malarial merozoites.
Staurosporine, a protein kinase inhibitor, inhibits the invasion of rhesus by Plasmodium knowlesi merozoites with an IC50 of 250 nM. The drug exerts its effects primarily on the merozoite, with little or no effect on the erythrocyte. Okadaic acid, an inhibitor of protein phosphatases, can partially abrogate the inhibitory effects of staurosporine. Staurosporine arrests invasion at a step which is ultrastructurally similar to the arrest caused by cytochalasins B and D: the merozoite attaches, apically reorients, and forms a junction with the erythrocyte, but it does not internalize. These results suggest that protein phosphorylation within the merozoite plays an important role in the internalization step of invasion.
Ward
G E
GE
Laboratory of Malaria Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Fujioka
H
H
Aikawa
M
M
Miller
L H
LH
D000470:Alkaloids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology* / Q000648:ultrastructure; D004988:Ethers, Cyclic / Q000494:pharmacology; D008253:Macaca mulatta; D008854:Microscopy, Electron; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D016790:Plasmodium knowlesi / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D019311:Staurosporine
D000470:Alkaloids; D004988:Ethers, Cyclic; D019319:Okadaic Acid; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine