Using Jensen's inequality to explain the role of regular calcium oscillations in protein activation.
Oscillations of cytosolic Ca(2 +) are very important for cellular signalling in excitable and non-excitable cells. The information of various extracellular stimuli is encoded into oscillating patterns of Ca(2 +) that subsequently lead to the activation of different Ca(2 +)-sensitive target proteins in the cell. The question remains, however, why this information is transmitted by means of an oscillating rather than a constant signal. Here we show that, in fact, Ca(2 +) oscillations can achieve a better activation of target proteins than a comparable constant signal with the same amount of Ca(2 +) used. For this we use Jensen's inequality that describes the relation between the function value of the average of a set of argument values and the average of the function values of the arguments from that set. We analyse the role of the cooperativity of the binding of Ca(2 +) and of zero-order ultrasensitivity, which are two properties that are often observed in experiments on the activation of Ca(2 +)-sensitive target proteins. Our results apply to arbitrary oscillation shapes and a very general decoding model, thus generalizing the observations of several previous studies. We compare our results with data from experimental studies investigating the activation of nuclear factor of activated T cells (NFAT) and Ras by oscillatory and constant signals. Although we are restricted to specific approximations due to the lack of detailed kinetic data, we find good qualitative agreement with our theoretical predictions.
Bodenstein
C
C
Department of Bioinformatics, Friedrich Schiller University Jena, Ernst-Abbe-Platz 2, D-07743 Jena, Germany. christian.bodenstein@uni-jena.de
Knoke
B
B
Marhl
M
M
Perc
M
M
Schuster
S
S
D000818:Animals; D020240:Apraxia, Ideomotor; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000378:metabolism; D013997:Time Factors; D018631:ras Proteins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D050778:NFATC Transcription Factors; D018631:ras Proteins; D002118:Calcium