A MAP kinase homologue from the human malaria parasite, Plasmodium falciparum

Doerig, Caroline; Parzy, Daniel; Langsley, Gordon; Horrocks, Paul; Carter, Richard; Doerig, Christian

doi:10.1016/0378-1119(96)00281-8

Cited by 59 publications

(47 citation statements)

References 26 publications

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“…Despite the presence of two MAPK-encoding genes, Pfmap-1 (6,12,15) and Pfmap-2 (7), the P. falciparum genome does not possess orthologues of the MAPK kinase (also called MEK, for MAP/ERK kinase) family (1,28), raising the question of the mode of activation of Pfmap-1 and Pfmap-2. PfPK7 (PlasmoDB database identifier PFB0605w) is the P. falciparum enzyme with the highest level of homology to MEKs (8).…”

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confidence: 99%

Disruption of the PfPK7Gene Impairs Schizogony and Sporogony in the Human Malaria ParasitePlasmodium falciparum

et al. 2008

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PfPK7 is an orphan protein kinase of Plasmodium falciparum with maximal homology to MEK3/6 and to fungal protein kinase A proteins in its C-terminal and N-terminal regions, respectively. We showed previously that recombinant PfPK7 is active on various substrates but is unable to phosphorylate the Plasmodium falciparum mitogen-activated protein kinase homologues, suggesting that it is not a MEK functional homologue. Using a reverse genetics approach to investigate the function of this enzyme in live parasites, we now show that PfPK7؊ parasite clones display phenotypes at two stages of their life cycle: first, a decrease in the rate of asexual growth in erythrocytes associated with a lower number of daughter merozoites generated per schizont, and second, a dramatic reduction in the ability to produce oocysts in the mosquito vector. A normal asexual growth rate and the ability to produce oocysts are restored if a functional copy of the PfPK7 gene is reintroduced into the PfPK7 ؊ parasites. Hence, PfPK7 is involved in a pathway that regulates parasite proliferation and development.

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confidence: 99%

Disruption of the PfPK7Gene Impairs Schizogony and Sporogony in the Human Malaria ParasitePlasmodium falciparum

et al. 2008

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“…), where the change of host (human to insect vector) results in parasite stage differentiation accompanied by changes in protein phosphorylation (11). The expression of a panoply of protein kinases and other signal transduction elements in Plasmodium gametocytes suggests that intracellular signaling pathways similar to those regulating cellular differentiation in other eukaryotes may operate during Plasmodium sexual development (4,(12)(13)(14).…”

Section: Box 1 Malaria Parasite Life Cycle (2 4)mentioning

confidence: 99%

“…Whether Plasmodium expresses an endogenous Epo-R is currently unknown, and available data do not establish whether the parasite responds directly to the hormone or not (the absence of Epo-R in reticulocytes and erythrocytes [26] may facilitate the search for a parasite-derived receptor). In contrast, two MAPK homologs of the ERK1/ERK2 subfamily have been found to be expressed in Plasmodium blood stages: Pfmap-1, which is found in both asexual parasites and gametocytes (14,27), and Pfmap-2, which appears to be expressed speci cally in gametocytes (28). The function of these enzymes in parasite development is not known; an attractive hypothesis is that one of them may transmit the sex determination signal from Epo to the nucleus.…”

Section: How Does Epo Mediate Plasmodium Sex Determination?mentioning

confidence: 99%

Erythropoiesis and Molecular Mechanisms for Sexual Determination in Malaria Parasites

2000

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SummaryMalaria parasites proliferate asexually within the vertebrate host but must undergo sexual reproduction for transmission to mosquitoes and hence infection of new hosts. The developmental pathways controlling gametocytogenesis are not known, but several protein kinases and other putative signal transduction elements possibly involved in this phenomenon have been found in Plasmodium. Recently, another developmental pathway, that of Plasmodium sex determination (male or female), has been shown to be triggered by erythropoiesis in the host. Rapid progress is being made in our understanding of the molecular basis of mammalian erythropoiesis, revealing kinase pathways that are essential to cellular responses triggered by the hormone erythropoietin. Although the molecular mechanisms whereby this hormone modulates the sex ratio of malaria parasites remain to be elucidated, it probably activates, within the parasite, transduction pathways similar to those found in other eukaryotes. Indeed, enzymes belonging to protein kinase families known to be involved in the response of mammalian cells to erythropoietin (such as the mitogen-activated protein kinases) have been identi ed in P. falciparum gametocytes. Some of these enzymes differ markedly from their mammalian homologs; therefore, identi cation of the transduction pathways of the parasite that are responsible for its developmental response to erythropoietin opens the way to the development of transmissionblocking drugs based on kinase inhibitors. IUBMB Life, 49: 245 -248, 2000

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“…Molecular cloning of MAPK-like proteins from Trypanosoma brucei (GenBank accession number Z54341) and P. falciparum (X82646 and X98689) have been reported. The P. falciparum MAPK-like kinase (X82646, 826 amino acids) has a long carboxyl-terminal tail consisting of nearly 460 amino acids (49). Yeast HOG1 (435 amino acids) also has an additional carboxyl terminus consisting of about 70 amino acids (12).…”

Section: Failure To Complement Yeast Hog1⌬ Mutant By Mrk-mentioning

confidence: 99%

Molecular Cloning and Expression of a Stress-responsive Mitogen-activated Protein Kinase-related Kinase from Tetrahymena Cells

Hisamoto

Sakai

Andoh³

et al. 1999

Journal of Biological Chemistry

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To identify genes responsive to cold stress, we employed the differential display mRNA analysis technique to isolate a novel gene from Tetrahymena thermophila which encodes a protein kinase of 430 amino acids. A homolog of this kinase with 90% amino acid sequence identity was also found in T. pyriformis. Both kinases contain 11 subdomains typical of protein kinases. Sequence analysis revealed that the predicted amino acid sequences resemble those of mitogen-activated protein kinase (MAPK), especially p38 and stressactivated protein kinase which are known to be involved in various stress responses. However, it should be noted that the tyrosine residue in the normally conserved MAPK phosphorylation site (Thr-X-Tyr) is replaced by histidine (Thr 226 -Gly-His 228 ) in this MAPKrelated kinase (MRK). The recombinant MRK expressed in Escherichia coli phosphorylated myelin basic protein (MBP) and became autophosphorylated. However, the mutated recombinant protein in which Thr 226 was replaced by Ala lost the ability to phosphorylate MBP, suggesting that Thr 226 residue is essential for kinase activity. The MRK mRNA transcript in T. thermophila increased markedly upon temperature downshift from 35 to 15°C (0.8°C/min). Interestingly, osmotic shock either by sorbitol (100 -200 mM) or NaCl (25-100 mM) also induced mRNA expression of the MRK in T. pyriformis. In addition, the activity of the kinase as determined by an immune complex kinase assay using MBP as a substrate was also induced by osmotic stress. This is the first demonstration of a MAPK-related kinase in the unicellular eukaryotic protozoan Tetrahymena that is induced by physical stresses such as cold temperature and osmolarity. The present results suggest that this MRK may function in the stress-signaling pathway in Tetrahymena cells.

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A MAP kinase homologue from the human malaria parasite, Plasmodium falciparum

Cited by 59 publications

References 26 publications

Disruption of the PfPK7Gene Impairs Schizogony and Sporogony in the Human Malaria ParasitePlasmodium falciparum

Disruption of the PfPK7Gene Impairs Schizogony and Sporogony in the Human Malaria ParasitePlasmodium falciparum

Erythropoiesis and Molecular Mechanisms for Sexual Determination in Malaria Parasites

Molecular Cloning and Expression of a Stress-responsive Mitogen-activated Protein Kinase-related Kinase from Tetrahymena Cells

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