ArticlePLoS biology2021
The 3-phosphoinositide-dependent protein kinase 1 is an essential upstream activator of protein kinase A in malaria parasites.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- A Novel Plasmodium berghei Protein, LSMP, Regulates Malaria Liver Stage Maturation.Molecular microbiology · 2026Article
- The Human Chk1 Inhibitor CHIR-124 Shows Multistage Activity against the Human Malaria ParasiteACS chemical biology · 2026Article
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- Article
- Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.Science advances · 2024Article
- Proteomic approaches for protein kinase substrate identification in Apicomplexa.Molecular and biochemical parasitology · 2024Review
- SPARK regulates AGC kinases central to theeLife · 2024Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
- SPARK regulates AGC kinases central to thebioRxiv : the preprint server for biology · 2024Article
- Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens.eLife · 2024Article
- Plasmodium falciparum GAP40 Plays an Essential Role in Merozoite Invasion and Gametocytogenesis.Microbiology spectrum · 2023Article
- Screening the Toxoplasma kinome with high-throughput tagging identifies a regulator of invasion and egress.Nature microbiology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signalling is essential for the proliferation of Plasmodium falciparum malaria blood stage parasites. The mechanisms regulating the activity of the catalytic subunit PfPKAc, however, are only partially understood, and PfPKAc function has not been investigated in gametocytes, the sexual blood stage forms that are essential for malaria transmission. By studying a conditional PfPKAc knockdown (cKD) mutant, we confirm the essential role for PfPKAc in erythrocyte invasion by merozoites and show that PfPKAc is involved in regulating gametocyte deformability. We furthermore demonstrate that overexpression of PfPKAc is lethal and kills parasites at the early phase of schizogony. Strikingly, whole genome sequencing (WGS) of parasite mutants selected to tolerate increased PfPKAc expression levels identified missense mutations exclusively in the gene encoding the parasite orthologue of 3-phosphoinositide-dependent protein kinase-1 (PfPDK1). Using targeted mutagenesis, we demonstrate that PfPDK1 is required to activate PfPKAc and that T189 in the PfPKAc activation loop is the crucial target residue in this process. In summary, our results corroborate the importance of tight regulation of PfPKA signalling for parasite survival and imply that PfPDK1 acts as a crucial upstream regulator in this pathway and potential new drug target.
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