These kinases fall into three groups based on the predicted extracellular domains ( 20).
histolytica TMK is predicted to contain an N-terminal signal sequence, an extracellular domain, and a single transmembrane helix followed by a cytosolic kinase domain.
More than 200 putative kinases, including an estimated 90 novel transmembrane kinases (TMKs), have been tentatively identified ( 20). histolytica was revealed by its genome analysis. The presence of an extensive signaling network in E. These pathways are mediated through a number of calcium binding proteins, including calmodulin ( 24), a novel calcium binding transcription regulator ( 11), and a novel protein involved in actin cytoskeletal dynamics ( 30). Signal transduction pathways involving calcium have also been identified ( 27, 28). The involvement of p 21-activated kinase in phagocytosis has also been demonstrated ( 17). For example, the binding of trophozoites to the extracellular matrix component collagen resulted in tyrosine phosphorylation of pp125 FAK and the recruitment of pp 60 src and paxillin to the pseudopods ( 26). The binding of extracellular matrix components to amoebae through focal adhesions is thought to be involved in generating signals needed for motility and cell killing ( 7, 12, 16, 19, 22, 23). It is likely that some of the signaling pathways play important roles in the host-parasite relationship.Ī number of signaling pathways have been reported in E. The diversity of these receptors helps organisms to interact with different extracellular signals and respond appropriately. These signals are perceived through an array of receptors present mainly on the cell surface. histolytica isolate into a virulent cell capable of tissue invasion.Īll living organisms have developed extensive mechanisms to respond to environmental signals. It is not yet clear what factor(s) or signal(s) is particularly involved in turning a commensal E. A large fraction of infected individuals do not display any symptoms of invasive disease and remain asymptomatic. It is endemic in many developing countries. The intestinal protozoan parasite Entamoeba histolytica is the causative organism of invasive amoebiasis, which is responsible for about 40,000 deaths every year ( 41). Our data indicate that the B1.I class of TMKs is involved in parasite proliferation. Inducible expression of the truncated TMK resulted in a decrease in cellular proliferation and an increase in sensitivity to serum starvation. An amoebic cell line expressing a truncated version of the B1.I.1 that lacked the kinase domain was generated. Staining was also seen in the frontal and posterior regions of the motile amoeba. Antisera generated against the extracellular domain of B1.I.1 stained the cell surface, particularly the areas of contact between the trophozoites. histolytica under the culture conditions used. Only two of the five full-length copies (B1.I.1 and B1.I.2) were expressed in E. However, the ligand binding domains of the orthologous B1 TMKs of the two species showed considerable divergence, indicating the possibility of a correlation with the pathogenic potential of the organism. BLAST analysis revealed the presence of homologs of these B1 TMKs in the nonpathogenic Entamoeba dispar.
EH MICROSYNTH SCHEMATIC FULL
Only five members were full length and contained both extracellular and cytosolic kinase domains. Genes corresponding to the majority of these were truncated and not considered for further analysis. Genomic sequencing revealed the presence of 28 members belonging to this family. Of these, the B1 family was chosen for further analysis.
histolytica, and these have been grouped into nine distinct families based on motifs present on both extracellular and kinase domains. The signaling proteome of Entamoeba histolytica is made of transmembrane kinases (TMKs) that are rarely found in unicellular eukaryotes.
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