 | COMBINATION OF BIPHASIC RESPONSE REGULATION AND POSITIVE FEEDBACK AS A GENERAL REGULATORY MECHANSIM IN HOMEOSTASIS AND SIGNAL TRANSDUCTION
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| | Andre Levchenko1)2), Jehoshua Bruck1) and Paul W. Sternberg2) |
| 1) Division of Engineering and Applied Science, California Institute of Technology
2) Division of Biology and Howard Hughes Medical Institute, California Institute of Technology |
| | In this report we introduce a mechanism of maintaining homeostasis (autoregulation) based on combination of a positive feedback and biphasic regulation. In this mechanism two molecular species interact in such a way that activation of the first of them affects activation of the second positively, while activation of the second species affects the activation of the first positively at low and negatively at high values. We demonstrate that a combination of biphasic response regulation with positive feedback leads to a possibility of homeostasis and limited graded response to variations of external parameters, possibly in a threshold-like manner. In addition, spike-like excitatory transient responses to perturbations of this system are possible. We then provide three examples of this sort of regulation in biological systems as diverse as transcriptional machinery, calcium channels and MAPK cascades. Correlation between biphasic response with positive feedback and functional characteristics of these three biological systems is then discussed. |
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