Role of Ca2+/calmodulin-PfPKB signaling pathway in erythrocyte invasion by Plasmodium falciparum.
Molecular mechanisms by which signaling pathways operate in the malaria parasite and control its development are promiscuous. Recently, we reported the identification of a signaling pathway in Plasmodium falciparum, which involves activation of protein kinase B-like enzyme (PfPKB) by calcium/calmodulin (Vaid, A., and Sharma, P. (2006) J. Biol. Chem. 281, 27126-27133). Studies carried out to elucidate the function of this pathway suggested that it may be important for erythrocyte invasion. Blocking the function of the upstream activators of this pathway, calmodulin and phospholipase C, resulted in impaired invasion. To evaluate if this signaling cascade controls invasion by regulating PfPKB, inhibitors against this kinase were developed. PfPKB inhibitors dramatically reduced the ability of the parasite to invade erythrocytes. Furthermore, we demonstrate that PfPKB associates with actin-myosin motor and phosphorylates PfGAP45 (glideosome-associated protein 45), one of the important components of the motor complex, which may help explain its role in erythrocyte invasion.
Vaid
Ankush
A
Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi-110067, India.
Thomas
Divya C
DC
Sharma
Pushkar
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D002147:Calmodulin; D008565:Membrane Proteins; D015800:Protozoan Proteins; C509918:glideosome-associated protein 45, Plasmodium falciparum; D011494:Protein Kinases; C487499:PKB protein, Plasmodium falciparum; D010738:Type C Phospholipases; D002118:Calcium