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.
Liu
Qing
Q
Laboratory of Molecular Signaling, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, England, UK.
Walker
Simon A
SA
Gao
Dingcheng
D
Taylor
James A
JA
Dai
Yan-Feng
YF
Arkell
Rebecca S
RS
Bootman
Martin D
MD
Roderick
H Llewelyn
HL
Cullen
Peter J
PJ
Lockyer
Peter J
PJ
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D011905:Genes, ras; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015290:Second Messenger Systems / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
C491144:RASA4 protein, human; D020703:ras GTPase-Activating Proteins; D049452:Green Fluorescent Proteins; D018631:ras Proteins; D002118:Calcium