Disruption of the PfPK7 gene impairs schizogony and sporogony in the human malaria parasite Plasmodium falciparum

Eukaryot Cell. 2008 Feb;7(2):279-85. doi: 10.1128/EC.00245-07. Epub 2007 Dec 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern
  • Blotting, Western
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology
  • Humans
  • Malaria, Falciparum / enzymology*
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / pathology
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / physiology*
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / growth & development
  • Protozoan Proteins / genetics
  • Protozoan Proteins / physiology*
  • Spores, Fungal / growth & development*

Substances

  • Protozoan Proteins
  • PK7 protein, Plasmodium falciparum
  • Mitogen-Activated Protein Kinase Kinases