Protein kinases, in response to signals, act as transducers through phosphorylation of specific proteins to control many metabolic and developmental events in cells. Protein phosphorylation/dephosphorylation is reported to play an important role during the development of Plasmodium falciparum in erythrocytes; and secondary messengers, such as cyclic AMP and GMP, have been linked to the sexual differentiation of parasites in erythrocytes and its subsequent development in the mosquito. We have focused on the:Cyclic GMP pathway - Cyclic GMP was suggested to be involved in modulating the gametogenesis of Plasmodium falciparum from intracellular gametocytes in the vertebrate host to extracellular gametes in the mosquito midgut. We previously identified a 1.1kbp cDNA clone homologous to the mammalian cyclic GMP-dependent protein kinase (cGK). Further attempts to isolate a full-length gene only yielded another partial cDNA clone with a about 1.8 kb insert. The deduced sequence from the cDNA contains one of two putative cGMP binding sites and consensus protein kinase domains. cGMP analogs have been selected which either activate or inhibit the cGK activity in gametocytes. Preliminary results indicate that a cGK inhibitor indeed prevents gametocytes from transforming into gametes in vitro. The precise role of cGK in parasite development will be further investigated.Other Protein kinases - Casein kinase I and II (CKI and CKII), and mitogen-activated protein kinase (MAPK) has been cloned. Plasmodium CKII appears to consist of only the catalytic subunit (40 kDa), which has been fully characterized, and not the regulatory subunit, as in mammalian CKII. The CKII activity can be detected when immunoprecipitated with antibody raised against PfCKII synthetic peptides. The strong homology (>60%) these kinases (CKI, CKII, and MAPK) share with their mammalian counterparts suggests that they may exhibit similar functions and may be critical for parasite development.
