{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Taylor HM"],"funding":["Medical Research Council","Wellcome Trust"],"pagination":["37-45"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2805293"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for > or =6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria."],"journal":["Eukaryotic cell"],"pubmed_title":["The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony."],"pmcid":["PMC2805293"],"funding_grant_id":["MC_U117532067","066742"],"pubmed_authors":["Baker DA","Hopp CS","McRobert L","Taylor HM","Dluzewski AR","Sicard A","Grainger M","Holder AA"],"additional_accession":[]},"is_claimable":false,"name":"The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony.","description":"A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for > or =6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Jan","modification":"2025-04-04T11:12:18.045Z","creation":"2019-03-27T00:27:53Z"},"accession":"S-EPMC2805293","cross_references":{"pubmed":["19915077"],"doi":["10.1128/ec.00186-09","10.1128/EC.00186-09"]}}