High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit Export

@article{citeulike:3484883, abstract = {10.1073/pnas.0807278105 We examined the effect of positive autoregulation on the steady-state behavior of the PhoQ/PhoP two-component signaling system in . We found that autoregulation has no effect on the steady-state output for a large range of input stimulus, which was modulated by varying the concentration of magnesium in the growth medium. We provide an explanation for this finding with a simple model of the PhoQ/PhoP circuit. The model predicts that even when autoregulation is manifest across a range of stimulus levels, the effects of positive feedback on the steady-state output emerge only in the limit that the system is strongly stimulated. Consistent with this prediction, amplification associated with autoregulation was observed in growth-limiting levels of magnesium, a condition that strongly activates PhoQ/PhoP. In a further test of the model, we found that strains harboring a phosphatase-defective PhoQ showed strong positive feedback and considerable cell-to-cell variability under growth conditions where the wild-type circuit did not show this behavior. Our results demonstrate a simple and general mechanism for regulating the positive feedback associated with autoregulation within a bacterial signaling circuit to boost response range and maintain a relatively uniform and graded output.}, author = {Miyashiro, Tim and Goulian, Mark}, citeulike-article-id = {3484883}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0807278105}, citeulike-linkout-1 = {http://www.pnas.org/content/0807278105v1//.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/0807278105v1//.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18987315}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18987315}, day = {5}, doi = {10.1073/pnas.0807278105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {applied-math, bio-stat, cell-models, control-theory, molecular-signaling, regulatory-cascades}, month = {November}, posted-at = {2008-12-29 19:55:41}, priority = {2}, title = {High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit}, url = {http://dx.doi.org/10.1073/pnas.0807278105}, year = {2008} }

TY - JOUR ID - citeulike:3484883 L3 - citeulike-article-id:3484883 N2 - 10.1073/pnas.0807278105 We examined the effect of positive autoregulation on the steady-state behavior of the PhoQ/PhoP two-component signaling system in . We found that autoregulation has no effect on the steady-state output for a large range of input stimulus, which was modulated by varying the concentration of magnesium in the growth medium. We provide an explanation for this finding with a simple model of the PhoQ/PhoP circuit. The model predicts that even when autoregulation is manifest across a range of stimulus levels, the effects of positive feedback on the steady-state output emerge only in the limit that the system is strongly stimulated. Consistent with this prediction, amplification associated with autoregulation was observed in growth-limiting levels of magnesium, a condition that strongly activates PhoQ/PhoP. In a further test of the model, we found that strains harboring a phosphatase-defective PhoQ showed strong positive feedback and considerable cell-to-cell variability under growth conditions where the wild-type circuit did not show this behavior. Our results demonstrate a simple and general mechanism for regulating the positive feedback associated with autoregulation within a bacterial signaling circuit to boost response range and maintain a relatively uniform and graded output. JF - Proceedings of the National Academy of Sciences TI - High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit KW - applied-math KW - bio-stat KW - cell-models KW - control-theory KW - molecular-signaling KW - regulatory-cascades AU - Miyashiro, Tim AU - Goulian, Mark PY - 2008/11/05/ UR - http://dx.doi.org/10.1073/pnas.0807278105 ER -