In D. melanogaster and C. ele gans, the MAPK pathways are involved in critical cellular and developmental processes. S. cerevi siae has four distinct MAPK signaling pathways that are likely mediators of responses to pheromone, nutritional starvation, and cellular or osmotic stress. The MAPK signaling pathways are well conserved in S. man Volasertib leukemia soni, Inhibitors,Modulators,Libraries including Inhibitors,Modulators,Libraries representatives of the subfami lies ERK, p38, JNK, and, NLK but lacks members of ERK5 that are part of a signaling pathways found mainly in mammals. Each subfamily is acti vated by different stimuli that generate different biologi cal responses. In S. mansoni only one protein was identified Inhibitors,Modulators,Libraries in JNK subfamily. JNK proteins play key roles in human cell function and in the development of C. elegans worms.
JNK may have an important role in schistosome survival and represent a good target for experimental approaches. STE group In S. mansoni, the STE group includes seven STE7, two STE11, and 13 STE20 kinases. The large number of STE family members in S. mansoni could translate into an enormous potential for down stream signal specificity and diversity. SmSLK is a Inhibitors,Modulators,Libraries Ste20 family protein, recently Inhibitors,Modulators,Libraries charac terized in S. mansoni, which is able to activate protein MAPK JNK in human embryonic kidney cells as well as in Xenopus oocytes. In addition, imunofluores cence showed that SmSLK was abundant in the tegu ment of adult schistosomes. These findings indicate that signals sensed in the environment by many differ ent proteins may activate the MAPK cascade that will generate an adaptive physiological response.
Futher more, molecules that activate the MAPK pathways, as some hormone and cytokine signals, are not found in the S. mansoni predicted proteome. It has been demonstrated that the parasite takes advantage of host proteins for its growth and development. Other ePKs such as members of the PKA, PKC, Raf and receptor protein tyrosine kinases kinase inhibitor MG132 families, also participate in MAPK signaling pathway. RTKs are anchored to the membrane and have an important role in transmitting the signal from the extracellular to cyto plasm. In C. elegans genome studies such as classical forward genetic and RNA interference screens and systematic targeted gene knockout revealed genes that are essential to the organism. Although the off target and non specific effect of RNAi, in S. mansoni this is one of the best approaches to explore the functional prop erty of the genes since the knockout experiments are not yet available for schistosomes. By analyzing the phylogenetic trees of the present work, it was possible to identify the proteins of S. mansoni that have homo logs in C. elegans and display lethality and sterile pheno types by RNAi.