RECEPTOR-DEPENDENT SENSITIVITY OF NF-κB TO LOW PHYSIOLOGICAL LEVEL

In the NFκB signaling pathway, cells respond to different concentrations of the TNFα signal by means of NFκB transcription factors. Previous studies showed that most cells are activated under high-dose stimulations and NFκB activation results in oscillations in nuclear NFκB abundance. Here, by analyzing sensitivity gain for the response of the nuclear NFκB to the number of cell-surface receptors under low-dose stimulations, we show that changes in the receptor number can give rise to significant changes in the nonsaturation part of the dose–response curve, where the receptor activation rates are very sensitive to stimulations. In addition, the number of the activated receptors tends to increase in a large range of stimulation dose and can significantly influence the expression of the downstream genes. These results imply that the number of cell-surface receptors plays a role of information encoding like frequency or amplitude encoding described in previous studies.