Cellular Signaling Paper

Cellular signaling has been a highly studied topic in biological and medical areas, being essential for many cellular processes. The efforts toward the comprehension of signaling pathways may help to understand a large range of molecular mechanisms such as those involved in host parasite interaction or in many types of cancer (Hanahan and Weinberg 2011). Cellular signaling is driven mainly by protein phosphorylation and dephosphorylation events, controlled by protein kinases and protein phosphatases, respectively. The identification of kinase and phosphatase substrates as well as the effects of each phosphorylation or dephosphorylation event on the cell are important steps to the understanding of several molecular signaling pathways. These
These protein kinases have the typical 11 kinase sub-domains and are involved in many cellular processes, such as cellular division, stress response, cellular differentiation, and others. MAPKs seem to have a special importance in Trypanosomatidae, a family of pathotogenic protozoan parasites that includes etiological agents of some important human illnesses: Leishmania major (leishmaniasis), Trypanosoma cruzi (Chagas disease) and Trypanosoma brucei (sleeping sickness). Trypanosomatids have a large number of MAPK-related genes in their genomes. This feature, associated with the complex life cycle of these parasites, possibly reflects a role of MAPK cascades in the responses to environmental cues (Parsons, Worthey et al. 2005). Several MAPKs were found to be activated in different forms of T. cruzi and T. brucei (Marchini, de Godoy et al. 2011; Urbaniak, Martin et al. 2013). Together with the fact that the majority of these kinases have no clear orthologues outside the trypanosomatids, reinforce the importance to better characterize MAPK pathways in these parasites. The few published works describe some MAPKs related to specific cellular processes, such as differentiation, proliferation and karyotype arrangement in T. brucei (Muller, Domenicali-Pfister et al. 2002; Ellis, Sarkar et al. 2004; Domenicali Pfister, Burkard et al. 2006). In L. mexicana, the participation of the MAPKs LmxMPK9 and LmxMPK4 in flagellar morphogenesis and in cellular viability, respectively, was observed (Bengs, Scholz et al. 2005; Wang, Melzer et al. 2005). Despite these efforts to the comprehension of MAPKs functions in trypanosomatids, there is no in vivo evidence about MAPKs targets or activators, the only reported MAP2K/MAPK interaction was observed in vitro for L. mexicana kinases (John von Freyend, Rosenqvist et al.