Positive Feedback Within a Kinase Signaling Complex Functions as a Switch Mechanism for NF-κB Activation

Abstract

Signaling Dynamics The signaling pathways that activate the transcription factor NF-κB are key regulatory pathways in cells of the immune system, and their dynamic properties are still being elucidated. In B cells, analysis of single-cell responses has shown that the stimulation of the B cell receptor causes a “digital” all-or-none response of cells to a stimulus. Shinohara et al. (p. 760 ) used a combination of mathematical modeling and experiments to show that this property of the system results from the presence of a positive feedback loop among the signaling components activated in response to the receptor. Studies in cells expressing mutated signaling components resolved key phosphorylation events that provide the threshold responses observed and identified potential molecular modifications that might modify the threshold or other aspects of the dynamic response.