The Ras binary switch: an ideal processor for decoding complex Ca2+ signals?

Abstract

Activation of cell-surface receptors often leads to changes in intracellular calcium concentration ([Ca(2+)](i)). Receptor-generated calcium transients are often seen as repetitive spikes of elevated intracellular calcium concentration ([Ca(2+)](i)), whose frequency varies according to the amplitude of the receptor stimuli. This suggests a requirement for molecular decoders, capable of interpreting such complex calcium signals into the correct physiological response. Ras proteins are binary molecular switches controlling a plethora of cellular responses. Whether Ras is in its active GTP-bound, or inactive GDP-bound, form is determined by the activity of guanine nucleotide exchange factors (GEFs) and GTPase-activating protein (GAPs). Calcium-regulated GEFs and GAPs have been identified, some with an exquisite sensitivity to [Ca(2+)](i), implicating a potential role of complex calcium signals in regulating Ras.