A secreted Plasmodium falciparum kinase reveals a signature motif for classification of tyrosine kinase-like kinases

Abdi, Abdirahman; Carvalho, Teresa G.; Wilkes, Jonathan M.; Doerig, Christian

doi:10.1099/mic.0.070409-0

Cited by 23 publications

(14 citation statements)

References 57 publications

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“…There is growing evidence that Plasmodium -infected erythrocytes secrete signalling molecules. Thus, an unbiased analysis of culture supernatants identified a protein phosphatase as well as PfTKL2, a member of the “Tyrosine kinase-like kinases” group [ 51 ]; this was corroborated by an independent study focussed on this enzyme [ 52 ]. Secretion of protein kinases to the culture medium has been observed in other parasitic eukaryotes, for example CK1 isoforms of Leishmania donovani promastigotes [ 53 ], and the catalytic subunit of another kinase, CK2, in the parasitic helminth Schistosoma mansoni [ 54 ].…”

Section: Discussionmentioning

confidence: 87%

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

et al. 2015

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Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion.

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Section: Discussionmentioning

confidence: 87%

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

et al. 2015

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“…There are also the following subfamilies of protein kinases: AGC, CaMK, CK1, CMGC, STE, TK and TKL (19–27) (Table I). …”

Section: Protein Kinasesmentioning

confidence: 99%

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Ardito

Giuliani

Perrone

et al. 2017

International Journal of Molecular Medicine

929

689

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Protein phosphorylation is an important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation and dephosphorylation events, by means of kinases and phosphatases. In particular, the protein kinases are responsible for cellular transduction signaling and their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors. Therefore, it is evident that the use of kinase inhibitors can be valuable for the treatment of cancer. In this review, we discuss the mechanism of action of phosphorylation, with particular attention to the importance of phosphorylation under physiological and pathological conditions. We also discuss the possibility of using kinase inhibitors in the treatment of tumors.

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“…It is possible that infection with P. falciparum induces a similar activation pathway that appears to be absent in B. divergens infections. A recent phosphoproteome analysis has led to the identification of several kinases that are secreted from P. falciparum into the RBC cytosol (Abdi et al, 2013;Nunes et al, 2010;Pease et al, 2013). It is possible that these kinases are involved in the activation or de-activation of host cell proteins, including the EAAT3 transporter.…”

Section: Inducible Glutamate Uptake Into Rbcmentioning

confidence: 98%

Novel insights into red blood cell physiology using parasites as tools

Baumeister

Gangopadhyay

Repnik

et al. 2015

European Journal of Cell Biology

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A secreted Plasmodium falciparum kinase reveals a signature motif for classification of tyrosine kinase-like kinases

Cited by 23 publications

References 57 publications

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

Novel insights into red blood cell physiology using parasites as tools

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