Differential processing of propeptide inhibitors of Rap phosphatases in Bacillus subtilis

In the phosphorelay signal transduction system for sporulation initiation i n Bacillus subtilis, the opposing activities of histidine kinases and aspar tyl phosphate phosphatases determine the cell's decision whether to continu e with vegetative growth or to initiate the differentiation process. Regula ted dephosphorylation of the Spo0A and Spo0F response regulators allows a v ariety of negative signals from physiological processes that are antithetic al to sporulation to impact on the activation level of the phosphorelay. Sp o0F similar to P is the known target of two related phosphatases, RapA and RapB. In addition to RapA and RapB, a third member of the Rap family of pho sphatases, RapE, specifically dephosphorylated the Spo0F similar to P inter mediate in response to competence development. RapE phosphatase activity wa s found to be controlled by a pentapeptide (SRNVT) generated from within th e carboxy-terminal domain of the phrE gene product. A synthetic PhrE pentap eptide could (i) complement the sporulation deficiency caused by deregulate d RapE activity of a phrE mutant and (ii) inhibit RapE-dependent dephosphor ylation of Spo0F similar to P in in vitro experiments. The PhrE pentapeptid e did not inhibit the phosphatase activity of RapA and RapB. These results confirm previous conclusions that the specificity for recognition of the ta rget phosphatase is contained within the amino acid sequence of the pentape ptide inhibitor.