CAPRI and RASAL Impose Different Modes of Information Processing on Ras Due to Contrasting Temporal Filtering of Ca2

• Published in: The Journal of cell biology Vol. 170; no. 2; pp. 183 - 190
• Main Authors: Liu, Qing, Walker, Simon A., Gao, Dingcheng, Taylor, James A., Dai, Yan-Feng, Arkell, Rebecca S., Bootman, Martin D., Roderick, H. Llewelyn, Cullen, Peter J., Lockyer, Peter J.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 18-07-2005; The Rockefeller University Press
• Subjects: Agonists; Animals; Calcium; Calcium - metabolism; Calcium Signaling - physiology; Cell lines; Cell Membrane - metabolism; Cell membranes; Cellular biology; CHO Cells; COS cells; Cricetinae; Cricetulus; Fluorescence; Genes, ras; Green Fluorescent Proteins - genetics; HeLa Cells; Histamines; Humans; Imaging; Kinetics; Protein Structure, Tertiary; Protein Transport; Proteins; ras GTPase-Activating Proteins - genetics; ras GTPase-Activating Proteins - metabolism; ras Proteins - genetics; ras Proteins - physiology; Second Messenger Systems - physiology
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200504167

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$Ca^{2+}-triggered$Ras GTPase-activating proteins. RASAL tracks agonist-stimulated Ca2+oscillations by repetitively associating with the plasma membrane, yet CAPRI displays a long-lasting$Ca^{2+}-triggered$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$Ca^{2+}-regulated$Ras deactivation.