PfeIK1, a eukaryotic initiation factor 2a kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation

Russo

Abstract

Background: Post-transcriptional control of gene expression is suspected to play an important role in malaria parasites. In yeast and metazoans, part of the stress response is mediated through phosphorylation of eukaryotic translation initiation factor 2a (eIF2a), which results in the selective translation of mRNAs encoding stress-response proteins.

Methods: The impact of starvation on the phosphorylation state of PfeIF2a was examined. Bioinformatic methods were used to identify plasmodial eIF2a kinases. The activity of one of these, PfeIK1, was investigated using recombinant protein with non-physiological substrates and recombinant PfeIF2a. Reverse genetic techniques were used to disrupt the pfeik1 gene.

Results: The data demonstrate that the Plasmodium falciparum eIF2a orthologue is phosphorylated in response to starvation, and provide bioinformatic evidence for the presence of three eIF2a kinases in P. falciparum, only one of which (PfPK4) had been described previously. Evidence is provided that one of the novel eIF2a kinases, PfeIK1, is able to phosphorylate the P. falciparum
eIF2a orthologue in vitro. PfeIK1 is not required for asexual or sexual development of the parasite, as shown by the ability of pfeik1- parasites to develop into sporozoites. However, eIF2a phosphorylation in response to starvation is abolished in pfeik1- asexual parasites

Conclusion: This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain but distinct regulatory domains, is conserved in P. falciparum.

Citation

Russo. (2009). PfeIK1, a eukaryotic initiation factor 2a kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation. Malaria Journal, 99 - 99. https://doi.org/10.1186/1475-2875-8-99

• Acceptance Date: May 12, 2009
• Publication Date: May 12, 2009
• Journal: Malaria Journal
• Publisher: Springer Verlag
• Pages: 99 - 99
• DOI: https://doi.org/10.1186/1475-2875-8-99
• Keywords: Catalytic Domain; Plasmodium Falciparum; Asexual Parasite; Amino Acid Starvation; Asexual Cycle
• Publisher URL: https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-8-99