ABSTRACT
Protein kinases are key regulators of many biochemical processes in eukaryotic cells. Malaria parasites, in spite of all their peculiarities, are not likely to represent an exception in this respect. Over the past few years, several genes encoding Plasmodium protein kinases have been cloned and characterized; these molecular studies extend previous data on kinase activities in parasite extracts. Here, Barbara Kappes, Christian Doerig and Ralph Graeser present available data on this topic, with an emphasis on cloned protein kinase genes, and discuss the potential outcome of such research in the context of drug development.
Subject(s)
Plasmodium falciparum/enzymology , Protein Kinases/genetics , Animals , CDC2 Protein Kinase/chemistry , CDC2 Protein Kinase/genetics , CDC2 Protein Kinase/physiology , Calcium-Calmodulin-Dependent Protein Kinases/chemistry , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Calcium-Calmodulin-Dependent Protein Kinases/physiology , Casein Kinases , Cyclic AMP-Dependent Protein Kinases/chemistry , Cyclic AMP-Dependent Protein Kinases/genetics , Cyclic AMP-Dependent Protein Kinases/physiology , Malaria, Falciparum/enzymology , Malaria, Falciparum/genetics , Mitogen-Activated Protein Kinase Kinases/chemistry , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/physiology , Plasmodium falciparum/genetics , Protein Kinases/chemistry , Protein Kinases/physiologyABSTRACT
Over the past few years, several reports have been published about the characterization of Plasmodium genes that are thought, on the basis of sequence homology with eukaryotic genes of known function, to be involved in the regulation of growth and differentiation of the parasite. Taken together with phenomenological observations on the regulation of developmental stages in the malaria life cycle, these data form the basis of an informative, albeit incomplete, picture of signal transtruction in Plasmodium. Christian Doerig here reviews Plasmodium elements that are presumably part of major regulatory pathways conserved in eukaryotes, and addresses the problem of how to pursue such studies beyond the stage of gene identification.
ABSTRACT
Pfmap-1, a gene encoding a novel protein kinase, has been identified in the human malaria parasite Plasmodium falciparum, using the polymerase chain reaction with degenerate oligodeoxyribonucleotides designed to hybridise to conserved regions of cdc2-related kinases. Computer comparison with other protein kinases strongly suggests that the protein encoded by this gene is closely related to mitogen-activated protein (MAP) kinases, which play important roles in eukaryotic adaptative response and signal transduction. In addition to the conserved MAP kinase catalytic domain, Pfmap-1 contains a highly charged C-terminal extension that includes two sets of repeated amino acid motifs. Pfmap-1 is located on chromosome 14 of P.falciparum, and its mRNA has a size of 3.7 kb.