Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast.
Bottom Line: Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca(2+).This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription.These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.
Affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Catalunya, Spain.Show MeSH
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Mentions: Prz1 activation and subcellular localisation are regulated by its phosphorylation state. In response to Ca2+ stimulation, Prz1 is dephosphorylated and activated (18). This activation can be monitored by a change in electrophoretic mobility, in addition to nuclear accumulation. We analysed the Prz1 protein in Δcmk1 cells and the mobility shift of Prz1 observed in wild-type cells is abolished in the absence of Cmk1 (Figure 5A). Moreover, we overexpressed Cmk1 and the inactive Cmk1-KA in wild-type cells. As Figure 5B shows, when Cmk1 was overexpressed, the Prz1 protein exhibited a slow electrophoretic-mobility which was absent with overexpression of Cmk1-KA, indicating that Prz1 is hyperphosphorylated when Cmk1 is overexpressed (Figure 5B).
Affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Catalunya, Spain.