ArticlePLoS biology2008
Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.
Article in PLoS biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments.Molecules (Basel, Switzerland) · 2020Pooled it
- TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.PLoS pathogens · 2026Article
- An orally available PfPKG inhibitor blocks Plasmodium's infection of the liver.PLoS pathogens · 2026Article
- Babesia divergens host cell egress is mediated by essential and druggable kinases and proteases.Nature microbiology · 2026Article
- Plasmodium falciparum gametogenesis essential protein 1 (GEP1) is a transmission-blocking target.FEBS letters · 2026Article
- An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP.Science advances · 2025Article
- Degradation of ribosomal RNA duringmBio · 2025Article
- Article
- Loss of serine/threonine protein phosphatase 6 severely impairs sexual stage development in malaria parasite Plasmodium berghei.PLoS pathogens · 2025Article
- Versatile Imidazole Scaffold with Potent Activity against Multiple Apicomplexan Parasites.ACS infectious diseases · 2025Article
- The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound.Nature microbiology · 2025Article
- Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis.Communications biology · 2025Article
- Advances in the dissection of Anopheles-Plasmodium interactions.PLoS pathogens · 2025Review
- Degradation of ribosomal RNA duringbioRxiv : the preprint server for biology · 2025Article
- The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole.PLoS pathogens · 2025Article
- 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
- Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation.PLoS biology · 2024Article
- The Cryptosporidium signaling kinase CDPK5 plays an important role in male gametogenesis and parasite virulence.Cell reports · 2024Article
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA), can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP) stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG) inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+) is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.