Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes.
Cell Microbiol
; 13(6): 836-45, 2011 Jun.
Article
en 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_malaria
/
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Plasmodium falciparum
/
Transducción de Señal
/
MAP Quinasa Quinasa 1
/
Eritrocitos
/
Quinasas p21 Activadas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suiza