PfPKB, a protein kinase B-like enzyme from Plasmodium falciparum: II. Identification of calcium/calmodulin as its upstream activator and dissection of a novel signaling pathway.
Intracellular cell signaling cascades of protozoan parasite Plasmodium falciparum are not clearly understood. We have reported previously (Kumar, A., Vaid, A., Syin, C., and Sharma, P. (2004) J. Biol. Chem. 279, 24255-24264) the identification and characterization of a protein kinase B-like enzyme in P. falciparum (PfPKB). PfPKB lacks the phosphoinositide-interacting pleckstrin homology domain present in mammalian protein kinase B. Therefore, the mechanism of PfPKB regulation was expected to be different from that of the host and had remained unknown. We have identified calmodulin (CaM) as the regulator of PfPKB activity. A CaM binding domain was mapped in the N-terminal region of PfPKB. CaM, in a calcium-dependent manner, interacts with this domain and activates PfPKB. CaM associates with PfPKB in the parasite and regulates its activity. Furthermore phospholipase C acts as an upstream regulator of this cascade as it facilitates the release of calcium from intracellular stores. This is one of the first multicomponent signaling pathways to be dissected in the malaria parasite.
Vaid
Ankush
A
Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi 110067, India.
Sharma
Pushkar
P
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010716:Phosphatidylinositols / Q000737:chemistry; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000502:physiology*; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000737:chemistry
D002147:Calmodulin; D010716:Phosphatidylinositols; D011494:Protein Kinases; C487499:PKB protein, Plasmodium falciparum; D010738:Type C Phospholipases; D002118:Calcium