Cross-talk between signaling pathways can generate robust oscillations in calcium and cAMP.
BACKGROUND
To control and manipulate cellular signaling, we need to understand cellular strategies for information transfer, integration, and decision-making. A key feature of signal transduction is the generation of only a few intracellular messengers by many extracellular stimuli.


RESULTS
Here we model molecular cross-talk between two classic second messengers, cyclic AMP (cAMP) and calcium, and show that the dynamical complexity of the response of both messengers increases substantially through their interaction. In our model of a non-excitable cell, both cAMP and calcium concentrations can oscillate. If mutually inhibitory, cross-talk between the two second messengers can increase the range of agonist concentrations for which oscillations occur. If mutually activating, cross-talk decreases the oscillation range, but can generate 'bursting' oscillations of calcium and may enable better filtering of noise.


CONCLUSIONS
We postulate that this increased dynamical complexity allows the cell to encode more information, particularly if both second messengers encode signals. In their native environments, it is unlikely that cells are exposed to one stimulus at a time, and cross-talk may help generate sufficiently complex responses to allow the cell to discriminate between different combinations and concentrations of extracellular agonists.
Siso-Nadal
Fernando
F
Gene Network Sciences, Cambridge, Massachusetts, United States of America.
Fox
Jeffrey J
JJ
Laporte
Stéphane A
SA
Hébert
Terence E
TE
Swain
Peter S
PS
D000495:Allosteric Site; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D009991:Oscillometry; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium