Bacterial cells can undergo asymmetric cell division. In Caulobacter crescentus, this involves the transition from a motile cell to an attached stalked cell, which divides to form a stalked cell that divides again immediately, and a motile swarmer cell that forms a flagellum and swims away before attaching and starting the process again. Two sensor histidine kinases, DivJ and PleC, are important for the polarized cell division process and determination of cell fate, and both phosphorylate and stimulate the activity of the diguanylate cyclase PleD, which produces cyclic-di-GMP. Paul et al. show that DivK, which is a response regulator downstream of both DivJ and PleC, is also an allosteric regulator of each enzyme. For PleC, which has both kinase and phosphatase activities, in vitro DivK and a nonphosphorylatable form of DivK stimulated the kinase activity and inhibited the phosphatase activity of PleC. In vitro, the activation of PleD by DivJ was inhibited by the addition of DivK because DivJ preferred DivK as a substrate. However, nonphosphorylatable DivK stimulated the kinase activity of DivJ for either wild-type DivK or PleD; thus, DivK is an allosteric regulator of both DivJ and PleC. Through the analysis of a DivK mutant that was defective in stimulating the kinase activity of PleC and analysis of PleC mutants defective in kinase activity, or kinase and phosphatase activity, the authors showed that, in vivo, the transition of PleC from a phosphatase to a kinase through the allosteric regulator DivK and the PleC-mediated activation of PleD were essential for the swarmer-to-stalk cell differentiation and asymmetric cell division. DivK appears to mediate crosstalk between and provide feedback to the DivJ and PleC kinases to coordinate polarized cell differentiation and division.
R. Paul, T. Jaeger, S. Abel, I. Wiederkehr, M. Folcher, E. G. Biondi, M. T. Laub, U. Jenal, Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate. Cell 133, 452-461 (2008). [PubMed]