Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability

• Published in: Current Opinion in Cell Biology Vol. 14; no. 2; pp. 140 - 148
• Main Author: Ferrell, James E
• Format: Book Review Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2002
• Subjects: Animals; bistable signalling system; Cdc2; CDC2 Protein Kinase - metabolism; Cell signalling; double-negative feedback; Enzyme Activation; Enzyme Stability; Escherichia coli; Feedback, Physiological - physiology; Female; JNK; JNK Mitogen-Activated Protein Kinases; MAPK; Mating Factor; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinases - metabolism; Oocytes - metabolism; Peptides - metabolism; positive feedback; Protein Engineering; Saccharomyces cerevisiae; Signal Transduction - physiology; Xenopus laevis; Cell signalling; positive feedback; bistable signalling system; Microbiology; JNK; Cell biology; Biochemistry; MAPK; double-negative feedback; Cdc2
• ISSN: 0955-0674; 1879-0410
• DOI: 10.1016/S0955-0674(02)00314-9

Cell signaling systems that contain positive-feedback loops or double-negative feedback loops can, in principle, convert graded inputs into switch-like, irreversible responses. Systems of this sort are termed ‘bistable’. Recently, several groups have engineered artificial bistable systems into
Escherichia coli and
Saccharomyces cerevisiae, and have shown that the systems exhibit interesting and potentially useful properties. In addition, two naturally occurring signaling systems, the p42 mitogen-activated protein kinase and c-Jun amino-terminal kinase pathways in
Xenopus oocytes, have been shown to exhibit bistable responses. Here we review the basic properties of bistable circuits, the requirements for construction of a satisfactory bistable switch, and the recent progress towards constructing and analysing bistable signaling systems.
The engineering and analysis of simple bistable signal transduction circuits is an important first step towards unravelling the logic of complex signaling networks.