Characterization of the cGMP-dependent protein kinase SmcGK1 of Schistosoma mansoni

Leutner, Silke; Beckmann, Svenja; Grevelding, Christoph G.

doi:10.1590/s0001-37652011000200023

Cited by 16 publications

(11 citation statements)

References 46 publications

(42 reference statements)

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“…Within the oviduct, however, which transports fertilized oocytes from the ovary to the ootype (the egg-forming organ of trematodes), an atypical oocyte congestion was observed. This finding pointed to an oocyte transport jam, which was explained by the decreasing motor activity of slomo males, which may support oocyte transport during the constant intimate pairing contact by peristaltic, wavelike movements of their muscular bodies [95].…”

Section: Pk Inhibitors With Anti-schistosomal Per-formance In Vitromentioning

confidence: 80%

“…Among these are a cAMP (3'-5'-cyclic adenosine monophsophate)-dependent protein kinase (PKA) of S. mansoni (SmPKA; [94]), the cGMP (cyclic guanosine-3', 5'-monophos-phate)-dependent protein kinase SmcGK1 [95], the p38 mitogen-activated protein kinase (MAPK) [96,97], the Src kinase SmTK3 [98], the Src/Fyn intermediate SmTK5 [71], the Fes homolog SmFes [99], the Syk kinase SmTK4 [100,101], the Src/Abl-hybrid kinase SmTK6 [100; 102], and the Abl-kinase homologs SmAbl1 and SmAbl2 [103]. First approaches towards the functional characterization of the schistosome homologs of PKA, cGK1, Src, Syk, and Abl kinases have been performed by inhibitor (see below) and/or RNA interference (RNAi) experiments.…”

Section: Kinase Signaling In Schistosomesmentioning

confidence: 99%

“…In Caenorhabditis elegans cGKs regulate growth processes, but also patterns of particular behavioral states such as locomotion [106,107]. In situhybridization experiments in adult schistosomes demonstrated a gonad-preferential expression profile of SmcGK1 in both genders indicating a putative role in reproduction [95].…”

Section: Kinase Signaling In Schistosomesmentioning

confidence: 99%

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Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

Beckmann

Leutner²,

Gouignard³

et al. 2012

cpd

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Schistosome parasites are the causative pathogens of schistosomiasis (bilharzia), a disease of worldwide significance. In terms of patient numbers, schistosomiasis ranks second to malaria as a parasitosis affecting more than 200 million people of the tropics and subtropics. Since the 1970s Praziquantel (PZQ) is the drug of choice and nearly exclusively used for treatment. However, drug resistance is an increasing threat, particularly with respect to large-scale PZQ administration programs. Last decade´s research indicated that resistance against PZQ can be induced under laboratory conditions, and field studies provided first indications for the possibility of reduced PZQ efficacy. Furthermore, clear evidence for the molecular armamentarium of schistosomes with multidrug transporters was found, one of which was responding to PZQ challenge. Also the development of a vaccine still represents an elusive goal, although effort and time have been invested in this subject. In light of these facts it is commonly accepted that new drugs are urgently needed. Research on signal transduction processes in Schistosoma mansoni has provided an unexpected and novel perspective towards this end. Molecular, biochemical, and physiological studies elucidating principles of schistosome development have demonstrated the essential role of protein kinases (PKs). In humans, PKs are known to be involved in cancer development. Since a variety of approved anticancer drugs targeting PKs exist, first studies have been performed to investigate whether these drugs are able to also inhibit schistosome PKs. Indeed, promising results have been obtained indicating the potential of PKs as privileged targets for new concepts in fighting schistosomes.

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Section: Pk Inhibitors With Anti-schistosomal Per-formance In Vitromentioning

confidence: 80%

Section: Kinase Signaling In Schistosomesmentioning

confidence: 99%

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Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

Beckmann

Leutner²,

Gouignard³

et al. 2012

cpd

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“…Here, Leutner et al (2011) by homology screening the parasite genome identify a number of members of the class of cGKs in S. mansoni, of which one is cloned and characterized. These authors provide first evidence that SmcGK1 is expressed in the gonads of male and female worms, and that antisense messages are transcribed from the same genomic locus in the same tissues, suggesting antisense regulation of this gene.…”

mentioning

confidence: 99%

“…These authors provide first evidence that SmcGK1 is expressed in the gonads of male and female worms, and that antisense messages are transcribed from the same genomic locus in the same tissues, suggesting antisense regulation of this gene. Furthermore, inhibitor studies in adult schistosomes in vitro indicate further roles of cGKs, probably associated with muscle activity (Leutner et al 2011). …”

mentioning

confidence: 99%

E Schistosoma mansoni at the molecular and cellular biology of helminth parasites VI meeting

Verjovski-Almeida

2011

An. Acad. Bras. Ciênc.

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Molecular information about eukaryotes has increased exponentially in the last decade. Sequencing of genomes and transcriptomes of model eukaryotic organisms has been followed by efforts in many groups to obtain equivalent information on helminth parasites. Large-scale molecular information is opening a door to understanding the intricate molecular and cellular biology of complex eukaryote parasites and raising the expectations to the ability of interfering with parasite-host interactions. Recognizing the need to increase the exchange of ideas in the area of helminth parasites, the international scientific community has gathered around a specialized meeting as early as 1997, when the first "Parasitic Helminths from Genomes to Vaccines" meeting took place in Edinburgh, UK, organized by Malcolm Kennedy from the University of Glasgow, and by Mark Blaxter and Rick Maizels, from the University of Edinburgh. A second meeting took place in Edinburgh in 1999, under the same title.In 2002 the event was renamed "Molecular and Cellular Biology of Helminth Parasites III" and it has been moved to the isle of Hydra, in Greece, where all subsequent events of the series have taken place. On September 5-10, 2010 the "Molecular and Cellular Biology of Helminth Parasites VI" meeting was organized by Kleoniki Gounaris and Murray Selkirk from the Imperial College, UK, and by Rick Maizels, from the University of Edinburgh. The meeting has an attendance limited to approximately 150 scientists, and the 2010 event comprised one keynote lecture, another 52 oral presentations with discussions in the mornings and evenings, and two poster sessions at night. We have invited several of the speakers who presented their work on Schistosoma mansoni to contribute articles to the Anais da Academia Brasileira de Ciências.In this volume, there are five contributions on S. mansoni. All of the authors have reviewed knowledge in the specific area of their work and have contributed novel results and/or novel perspectives on their subjects of study. Evidence of non-coding RNA expression in S. mansoni is reviewed by Oliveira et al. (2011). This is an example of analysis that has only been possible because of the combined availability of the parasite genome sequence (Berriman et al. 2009) and of large scale transcriptome data which was pioneered by Franco et al. (1997) and considerably extended by Verjovski-Almeida et al. (2003). Among other topics, these authors map all publicly available ESTs to the genome sequence, thus identifying those long (> 200 nt) non-coding RNAs transcribed from the opposite strand of protein-coding genes and provide microarray data on the differential expression of long non-coding RNAs in different life cycle stages of the parasite (Oliveira et al. 2011).Serpins or serine protease inhibitors are a structurally conserved family of macromolecular inhibitors found in virtually all biological systems. Quezada and McKerrow (2011) give here another very interesting example as to how the completion and annotation of the genomes of S. m...

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Derivatives of biarylalkyl carboxylic acid induce pleiotropic phenotypes in adult Schistosoma mansoni in vitro

et al. 2016

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Schistosomes and other parasitic platyhelminths cause infectious diseases of worldwide significance for humans and animals. Despite their medical and economic importance, vaccines are not available and the number of drugs is alarmingly limited. For most platyhelminths including schistosomes, Praziquantel (PZQ) is the commonly used drug. With respect to its regular application in mass treatment programs, however, there is increasing concern about resistance development.Previous studies demonstrated that inhibitors used to treat non-parasitic human diseases may be useful to be tested for their effects on parasites. To this end, we focused on biarylalkyl carboxylic acids (BACAs) as basis, which had been shown before to be interesting candidates in the context of finding alternative approaches to treat diabetes mellitus. We tested 32 chemically modified derivatives of these substances (biarylalkyl carboxylic acid derivatives (BACADs)) for their effects on adult Schistosoma mansoni in vitro. Treatment with 18 BACADs resulted in egg production-associated phenotypes and reduced pairing stability. In addition, 12 of these derivatives affected vitality and/or caused severe tegument damage, gut dilatation, or other forms of tissue disintegration which led to the death of worms. In most cases (10/12), one derivative caused more than one phenotype at a time. In vitro experiments in the presence of serum albumin (SA) and alpha-acidic glycoprotein (AGP) indicated a varying influence of these blood components on the effects of two selected derivatives. The variety of observed phenotypes suggested that different targets were hit. The results demonstrated that BACADs are interesting substances with respect to their anti-schistosomal effects.

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Characterization of the cGMP-dependent protein kinase SmcGK1 of Schistosoma mansoni

Cited by 16 publications

References 46 publications

Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

Protein Kinases as Potential Targets for Novel Anti-Schistosomal Strategies

E Schistosoma mansoni at the molecular and cellular biology of helminth parasites VI meeting

Derivatives of biarylalkyl carboxylic acid induce pleiotropic phenotypes in adult Schistosoma mansoni in vitro

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