Stress responses of the unicellular cyanobacterium Synechocystis involve several regulatory systems, including two-component ones, and negative supercoiling of genomic DNA. The role of serine/threonine protein kinases (STPKs) in the cold response was studied in Synechocystis. A screening of a collection of STPK mutants identified four enzymes - SpkB, SpkD, SpkE, and SpkG - as possible transcriptional regulators at lower temperatures. A proteome analysis in a SpkE Synechocystis mutant implicated SpkE in the formation of the protein pattern. In vitro phosphorylation assays of recombinant SpkE confirmed that the STPK was functionally active and utilized basic proteins as preferable substrates.