It must be noted that the patients recruited here were drug naive, and received no treatment

nregulates PDH activity by phosphorylation of the E1 subunit. The status of PDH in E. cuniculi is currently somewhat equivocal, since the microsporidian has two E1 subunit homologues but no evident E2 or E3 component, and the E2 component is critical for regulating PDH kinase activity. Thus without a complete PDH complex there is probably no need for a PDH kinase. With the exception of one of its two PDH kinases, budding yeast aPKs all show clear orthologous relationships to their fission yeast counterparts. Protein kinase accessory domains Only 2 ePKs belonging to the AGC family were found to contain readily identifiable domains in addition to the kinase catalytic domain. These are the protein kinase Cterminal domain and the protein kinase C phorbol ester/diacylglycerolbinding domain. The microsporidian PKA presents the domain architecture NH3 +-kinase-PF00433-CO2 -. The protein kinase C-terminal domain is found in a AVE8062A web variety of proteins with different functions and dependencies, and so per se it is not useful for assigning putative function. The AGC kinase CAD25005.1 presents the domain organisation NH3 +kinasePF00433PF00130-CO2 -. Protein kinase-regulating proteins Only two cyclins were found in the E. cuniculi genome. One instance of the regulatory subunit of Casein Kinase II was also found, plus two regulatory subunits of PKA. allows for more complex regulation networks. Thus, protein shortening in E. cuniculi may reflect reduced proteinprotein interactions as a result of various gene losses linked to the intracellular parasitic nature. The kinome of E. cuniculi, consisting of only 32 protein kinases, is a good illustration of this hypothesis. The microsporidian kinome is approximately one fourth the size of the kinomes of S. cerevisiae and S. pombe. The E. cuniculi kinome has underscored the importance of a number of protein kinases that are involved in essential cellular processes and likely to be essential to all eukaryotes. Therefore, the microsporidian presents an opportunity for evaluating the basic aspects of the most fundamental cellular mechanisms as mediated by protein kinases. The E. cuniculi kinome includes what might be considered as a core set of protein kinases required for performing the cell division cycle: a Cdc28p/Cdc2 cyclin-dependent kinases to regulate progression through different cell cycle stages, its negative regulator, a DDK to trigger initiation of DNA replication, a polo kinase an Aurora kinase to orchestrate various aspects of cell division, a TTK for spindle pole duplication and homologues of Te1lp and Chk1p for regulation in response to DNA damage and/or stalled replication forks. A second CDK might also function as a CDK-activating kinase, and the Bud32p orthologue may be needed for telomere maintenance. Kinases involved specifically and fundamentally in cell cycle regulation may therefore represent ~30% of the E. cuniculi kinome, and orthologues of all the critical activities appear to be present with the exception of those that form part of the fungal MEN/SIN pathways. In contrast, E. cuniculi appears to lack almost all of the protein kinases involved in stress responses, ion homeostasis and nutrient signalling. Although it has orthologues of PKA and DYRK, there is a complete lack of MAP kinase pathways and many other kinases involved in these signalling routes. Most notable by their absence are TOR and AMPK, and E. cuniculi may be the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19793655 first eukaryote in which neither of these conserved functions i