The second messenger calcium plays a key role in conveying specificity of 
signaling pathways in plant cells. Specific calcium signatures are decoded to 
generate correct gene expression responses and amplification of calcium 
signatures is vital to this process. (1) It is not known if this amplification 
is an intrinsic property of all calcium-regulated gene expression responses and 
whether all calcium signatures have the potential to be amplified, or (2) how a 
given calcium signature maintains specificity in cells containing a great number 
of transcription factors (TFs) and other proteins with the potential to be 
calcium-regulated. The work presented here uncovers the design principle by 
which it is possible to decode calcium signals into specific changes in gene 
transcription in plant cells. Regarding the first question, we found that the 
binding mechanism between protein components possesses an intrinsic property 
that will nonlinearly amplify any calcium signal. This nonlinear amplification 
allows plant cells to effectively distinguish the kinetics of different calcium 
signatures to produce specific and appropriate changes in gene expression. 
Regarding the second question, we found that the large number of calmodulin 
(CaM)-binding TFs or proteins in plant cells form a buffering system such that 
the concentration of an active CaM-binding TF is insensitive to the 
concentration of any other CaM-binding protein, thus maintaining specificity. 
The design principle revealed by this work can be used to explain how any 
CaM-binding TF decodes calcium signals to generate specific gene expression 
responses in plant cells via transcription.