Functional modules in biological signalling networks.
Signalling pathways carry information from the outside of the cell to cellular machinery capable of producing biochemical or physiological responses. Although linear signalling plays an important role in biological regulation, signalling pathways are often interconnected to form networks. We have used computational analysis to study emergent properties of simple networks that consist of up to four pathways, We find that when one pathway gates signal flow through other pathways which produce physiological responses, gating results in signal prolongation such that the signal may be consolidated into a physiological response. When two pathways combine to form a feedback loop such feedback loops can exhibit bistability. Negative regulators of the loop can serve as the locus for flexibility whereby the system has the capability of switching states or functioning as a proportional read-out system. Networks where bistable feedback loops are connected to gates can lead to persistent signal activation at distal locations. These emergent properties indicate system analysis of signalling networks may be useful in understanding higher-order biological functions.
Bhalla
U S
US
National Centre for Biological Sciences, Bangalore, India.
Iyengar
R
R
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases