CAPRI and RASAL impose different modes of information processing on Ras due to contrasting temporal filtering of Ca²⁺

The versatility of Ca²⁺ as a second messenger lies in the complex manner in which Ca²⁺ signals are generated. How information contained within the Ca²⁺ code is interpreted underlies cell function. Recently, we identified CAPRI and RASAL as related Ca²⁺-triggered Ras GTPase-activating proteins. RASAL tracks agonist-stimulated Ca²⁺ oscillations by repetitively associating with the plasma membrane, yet CAPRI displays a long-lasting Ca²⁺-triggered translocation that is refractory to cytosolic Ca²⁺ oscillations. CAPRI behavior is Ca²⁺- and C2 domain–dependent but sustained recruitment is predominantly Ca²⁺ independent, necessitating integration of Ca²⁺ by the C2 domains with agonist-evoked plasma membrane interaction sites for the pleckstrin homology domain. Using an assay to monitor Ras activity in real time, we correlate the spatial and temporal translocation of CAPRI with the deactivation of H-Ras. CAPRI seems to low-pass filter the Ca²⁺ signal, converting different intensities of stimulation into different durations of Ras activity in contrast to the preservation of Ca²⁺ frequency information by RASAL, suggesting sophisticated modes of Ca²⁺-regulated Ras deactivation.