Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes.
Cell Microbiol
; 13(6): 836-45, 2011 Jun.
Article
in En
| MEDLINE
| ID: mdl-21371233
ABSTRACT
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 malaria pathogenesis. Here, we report that a protein kinase-mediated signalling pathway involving host RBC PAK1 and MEK1, which do not have orthologues in the Plasmodium kinome, is selectively stimulated in Plasmodium falciparum-infected (versus uninfected) RBCs, as determined by the use of phospho-specific antibodies directed against the activated forms of these enzymes. Pharmacological interference with host MEK and PAK function using highly specific allosteric inhibitors in their known cellular IC50 ranges results in parasite death. Furthermore, MEK inhibitors have parasiticidal effects in vitro on hepatocyte and erythrocyte stages of the rodent malaria parasite Plasmodium berghei, indicating conservation of this subversive strategy in malaria parasites. These findings have profound implications for the development of novel strategies for antimalarial chemotherapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Signal Transduction
/
MAP Kinase Kinase 1
/
Erythrocytes
/
P21-Activated Kinases
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Microbiol
Journal subject:
MICROBIOLOGIA
Year:
2011
Document type:
Article
Affiliation country:
Suiza