The Plasmodium Kinome

Defined operationally as those kinases related to the CDK, MAPK, GSK3 and CLK families, this is the largest family of kinases in the Plasmodium kinome with 26 representatives in P. falciparum. With recognisable representatives of each sub-family of the greater CMGC family, (namely CDK [5 members], GSK3 [3 members], MAPK [2 members], CLK [4 members]), the pivotal role played by members of this family is underscored by the demonstration of apparent essentiality for most of these kinases in the P. berghei knock out study.15 

The NIMA related kinases (Nek) family has four members in the P. falciparum kinome (Pfnek-1, Pfnek-2, Pfnek-3 and Pfnek-4). In other Eukaryotic systems these enzymes appear to play important roles in cell division, including 

Furthermore, and quite unexpectedly, recent studies (Cooke, personal communication) now indicate that a subset of FIKK genes are refractory to genetic deletion and are therefore likely to be directly involved in essential metabolic or other processes that are vital for parasite survival. 

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A remarkable genetic study of the function of all of the members of the Plasmodium kinome has recently been completed by Tewari, Billker and coworkers.15 Whilst such a study, if carried out in a human Plasmodium species (e.g. P. falciparum or P. vivax) would be limited by being applicable to the erythrocytic phase of the life cycle, Tewari and co-workers used the rodent species, P. berghei, which permitted an analysis of the effects of each kinase knock-out in both asexual and sexual stages of the life cycle. As noted... 

Similar screening exercises from other compound collections have successfully revealed additional target classes,53 though in these studies the more difficult path of in vitro testing combined with the absence of a broad kinase screen for the Plasmodium kinome means that this class of targets is... 

Plasmodium falciparum the kinome of a divergent eukaryote. BMC Genomics 5 79... 

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