At the time of our first report, we hypothesized that SSCMKI was needed for the phosphorylation of proteins involved in the regulation of the cell see more cycle and/or for the phosphorylation and activation of transcription factors needed

for the dimorphic transitions of the fungus. However, we mentioned that the final interpretation of our results awaited the identification of the interacting partners of SSCMKI that was also accomplished in this work. Important information related to the role of SSCMK1 in S. schenckii, was obtained with the yeast two-hybrid assay. Among the many proteins identified as interacting with SSCMK1 we identified a S. schenckii homologue of HSP90. This interaction was corroborated with Co-IP. It is a well-known fact that all organisms from bacteria to higher eukaryotes respond to elevated temperatures

by producing heat shock proteins. Two important observations Selleck VS-4718 CP673451 clinical trial regarding a connection between the heat shock response and CaMKs have been reported. In C. albicans, this kinase was shown to have a role in the capacity of fungal cells to grow at elevated temperature [48] and in Arabidopsis thaliana, CaMK-3 has been observed to be part of the heat shock response, possibly by the phosphorylation of the heat shock response factor and the induction of the transcription of the heat shock proteins [49]. In tomato (Solanum lycopersicum), LeCPK2, a CaMK, is up regulated in response to heat stress [50]. Heat shock proteins are a widespread family of molecular chaperones found in bacteria and all eukaryotic organisms. These chaperones

ensure both the folding of newly synthesized proteins and their refolding under denaturing stress conditions [51]. HSP90 has been reported to interact with protein kinases. Specifically during the cell cycle, HSP90 has been reported to intervene, together with cdc37, in the stabilization of the monomeric cdk4, prior to its interaction with cyclin D [16]. It has also been reported to interact with the protein phosphatase, calcineurin that dephosphorylates CaMKs [52, 53]. The interaction of HSP90 with protein kinases occurs at the N terminal domain of the HSP and two hypotheses has been postulated regarding the role of this HSP in the activity of protein kinases. HSP90 could facilitate the activation of the protein kinases by the induction of a conformational change Loperamide in these kinases or could maintain the phosphorylated kinases sequestered until needed [52]. Nevertheless, SSCMK1 binds to the C terminal domain of SSHSP 90 where effectors of this heat shock protein interact. This domain starts with amino acid D621 in the human homologue of HSP90. This suggests that instead of HSP90 regulating SSCMK1, the kinase could in some form or another be regulating HSP90. If this were correct, lowering the levels of SSCMK1 would affect the function of HSP90 and in turn render the cells intolerant to high temperatures as was observed by us.