The epidermal growth factor receptor (EGF-R) plays an important role in development and cell differentiation, homologues of EGF-R have been identified a broad range vertebrate invertebrate organisms. This work concerns the functional characterization SER, EGF-R-like molecule previously helminth parasite Schistosoma mansoni (Shoemaker, C. B., Ramachandran, H., Landa, A., dos Reis, M. G., Stein, L. D. (1992) Mol. Biochem. Parasitol. 53, 17–32). Transactivation assays performed epithelial...

Background Alveolar echinococcosis (AE) is a life-threatening disease caused by larvae of the fox-tapeworm Echinococcus multilocularis. Crucial to AE pathology continuous infiltrative growth parasite's metacestode stage, which driven population somatic stem cells, called germinative cells. Current anti-AE chemotherapy using benzimidazoles ineffective in eliminating cell population, thus leading remission parasite upon therapy discontinuation. Methodology/Principal findings We herein describe...

Schistosome parasites cause schistosomiasis, one of the most prevalent parasitemias worldwide affecting humans and animals. Constant pairing schistosomes is essential for female sexual maturation egg production, which causes pathogenesis. Female involves signaling pathways controlling mitosis differentiation within gonads. In vitro studies had shown before that a Src-specific inhibitor, Herbimycin A (Herb A), TGFβ receptor (TβR) inhibitor (TRIKI) have physiological effects such as suppressed...

The Venus kinase receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine domain close to that insulin and extracellular Flytrap (VFT) structure similar the ligand binding many class C G protein coupled receptors. This (RTK) was first discovered in platyhelminth parasite Schistosoma mansoni, then large variety invertebrates. A vkr gene found most genomes, except S. mansoni which two genes Smvkr1 Smvkr2 exist. VKRs form unique family RTKs present only...

Background Chemotherapy of schistosomiasis relies on a single drug, Praziquantel (PZQ) and mass-use this compound has led to emergence resistant strains Schistosoma mansoni, therefore pointing out the necessity find alternative drugs. Through their essential functions in development metabolism, receptor tyrosine kinases (RTK) could represent valuable drug targets for novel anti-schistosome chemotherapies. Taking advantage similarity between catalytic domains S. mansoni insulin receptors...

Background Alveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of tapeworm Echinococcus multilocularis. The infection characterized tumour-like growth within host liver, leading to extensive fibrosis and organ-failure. molecular mechanisms parasite organ tropism towards liver influences cytokines hormones on development are little studied date. Methodology/Principal findings We show that E. multilocularis larval stage expresses three members fibroblast factor...

Cellular protein-tyrosine kinases play key roles in signal transduction processes eukaryotes. SmTK4 was the first Syk kinase identified a parasite and found to be tissue-specifically transcribed gonads of adult Schistosoma mansoni. Functional analyses confirmed its role oogenesis spermatogenesis. As an upstream binding partner, cellular SmTK6 isolated from yeast two-hybrid library. Phylogenetic performed this study suggestions hybrid character SmTK6. Biochemical studies made Xenopus oocytes...

One of the focal subjects in insulin delivery is development formulations that protect native from degradation under acidic pH stomach. In this work we show, for first time, a graphene oxide (GO) based matrix can ensure stability at low pH. GO and modified with 2-nitrodopamine coated magnetic particle (GO–MPdop) matrices loaded were prepared triggered release was studied. The loading on nanomaterials proved to be extremely high < 5.4 capacity 100 ± 3% 88 GO–MPdop. insulin-containing stable...

Among biosensors, genetically-encoded FRET-based biosensors are widely used to localize and measure enzymatic activities. Kinases activities of particular interest as their spatiotemporal regulation has become crucial for the deep understanding cell fate decisions. This is especially case ERK, whose activity a key node in signal transduction pathways can direct into various processes. There constant need better tools analyze kinases vivo, detect even slightest variations Here we report...

Protein kinases (PKs) are one of the largest protein families in most eukaryotic organisms. These enzymes involved control cell proliferation, differentiation and metabolism a large number anticancer drugs currently used directed against PKs. The structure function PKs well conserved throughout evolution. In schistosome parasites, were shown to be essential functions at every stage parasite life cycle, making these promising anti-parasite drug targets. this study, we tested panel commercial...

In the search for new strategies to fight schistosomiasis, unique reproductive biology of Schistosoma mansoni has come into focus research. The development gonads and ability egg production are fundamental not only continuing life cycle but also pathogenicity. Previous studies schistosome demonstrated an influence pairing on gonad female gene expression profiles in both genders. Due limited access specific tissues, however, most these were done at level whole worms neglecting individual...

Background Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ) is only drug widely used for controlling schistosomiasis. The absence a vaccine and fear PZQ resistance have motivated search alternatives. Studies on protein kinases (PKs) demonstrated their importance diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 SmAbl2, were identified Schistosoma mansoni shown to...

Abstract Background It is clear that the coordinated and reciprocal actions of kinases phosphatases are fundamental in regulation development growth malaria parasite. Protein Phosphatase type 1 a key enzyme playing diverse essential roles cell survival. Its dephosphorylation activity/specificity governed by interaction its catalytic subunit (PP1c) with regulatory proteins. Among these, inhibitor-2 (I2) one most evolutionarily ancient PP1 regulators. In vivo studies various organisms revealed...

Xenopus oocytes expressing fibroblast growth factor receptor 1 (FGFR1) were used as a biological model system to analyse the signal transduction pathways that are triggered by (FGF1). Germinal vesicle breakdown (GVBD) and phosphorylation of extracellular signal‐regulated protein kinase 2 (ERK2) occured 15 h after FGF1 addition. These events Ras‐dependent they blocked Ras dominant negative form. The activity was promoted three upstream effectors, factor‐bound (Grb2), phosphatidylinositol...

Grb14 is a member of the Grb7 family adapters and acts as negative regulator insulin-mediated signaling. Here we found that protein kinase Czeta (PKCzeta) interacting protein, ZIP, interacted with Grb14. Coimmunoprecipitation experiments demonstrated ZIP bound to both PKCzeta, thereby acting link in assembly PKCzeta-ZIP-Grb14 heterotrimeric complex. Mapping studies indicated through its ZZ zinc finger domain phosphorylated insulin receptor region (PIR) PKCzeta under vitro conditions CHO-IR...

The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential regulator cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role cycle control appears to be mediated through activation phosphatase type 1 (PP1) Schizosaccharomyces pombe. We have identified Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs leucine-rich repeat family. showed by glutathione-S-transferase pull-down assay that gene product...

In all metazoa, the response of cells to molecular stimuli from their environment represents a fundamental principle regulatory processes controlling cell growth and differentiation. Among membrane-linked receptors mediating extracellular communication are integrin receptors. Besides managing adhesion matrix or other cells, they arrange information flow into by activating intracellular signaling pathways often acting synergistically through cooperation with factor Although wealth exists on...

Topoisomerases, targets of inhibitors used in chemotherapy, induce DNA breaks accumulation leading to cancer cell death. A newly synthesized copper(II) indenoisoquinoline complex WN197 exhibits a cytotoxic effect below 0.5 µM, on MDA-MB-231, HeLa, and HT-29 cells. At low doses, inhibits topoisomerase I. higher it IIα IIβ, displays intercalation properties. damage is detected by the presence γH2AX. The activation Damage Response (DDR) occurs through phosphorylation ATM/ATR, Chk1/2 kinases,...

Polo-like kinases (Plks) are a family of conserved regulators variety events throughout the cell cycle, expanded from one Plk in yeast to five Plks mammals (Plk1-5). Plk1 is best characterized member family, homolog founding Polo Drosophila, and plays major role cycle progression by triggering G2/M transition. Plk4/Sak (for Snk (Serum-inducible kinase) akin unique structurally distinct other members, with essential functions centriole duplication. The genome trematode parasite Schistosoma...