Calcium regulates ERK signaling by modulating its protein-protein interactions.

Intracellular transmission of extracellular signals is mediated by a complex network of second messengers, interacting proteins and signaling cascades that cumulatively govern essentially all stimulated cellular processes. Two important signaling components in the network are the extracellular signal-regulated kinase (ERK) signaling cascade and elevation of calcium concentrations, which transmit signals of hormones, growth factors and other ligands. Each of these components is known to independently regulate a large number of targets in various cellular organelles. The cooperation between them, however, seems to modulate the fate of their individual signals, and accordingly, their regulated processes. We have recently shown that calcium modulates the protein interaction properties of ERKs, which further affect the subcellular localization of the latter and as a consequence also the distribution of their targets. These effects of calcium are important in determining the specificity of the ERK cascade, and thereby, play important roles in the regulation of ERK-dependent cellular processes. Our findings, as well as their possible implications, are further discussed in this addendum.