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Identification of a Ras GTPase‐activating protein regulated by receptor‐mediated Ca 2+ oscillations
Author(s) -
Walker Simon A,
Kupzig Sabine,
Bouyoucef Dalila,
Davies Louise C,
Tsuboi Takashi,
Bivona Trever G,
Cozier Gyles E,
Lockyer Peter J,
Buckler Alan,
Rutter Guy A,
Allen Maxine J,
Philips Mark R,
Cullen Peter J
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600197
Subject(s) - biology , gtpase , identification (biology) , microbiology and biotechnology , gtpase activating protein , receptor , signal transduction , g protein , computational biology , biochemistry , ecology
Receptor‐mediated increases in the concentration of intracellular free calcium ([Ca 2+ ] i ) are responsible for controlling a plethora of physiological processes including gene expression, secretion, contraction, proliferation, neural signalling, and learning. Increases in [Ca 2+ ] i often occur as repetitive Ca 2+ spikes or oscillations. Induced by electrical or receptor stimuli, these repetitive Ca 2+ spikes increase their frequency with the amplitude of the receptor stimuli, a phenomenon that appears critical for the induction of selective cellular functions. Here we report the characterisation of RASAL, a Ras GTPase‐activating protein that senses the frequency of repetitive Ca 2+ spikes by undergoing synchronous oscillatory associations with the plasma membrane. Importantly, we show that only during periods of plasma membrane association does RASAL inactivate Ras signalling. Thus, RASAL senses the frequency of complex Ca 2+ signals, decoding them through a regulation of the activation state of Ras. Our data provide a hitherto unrecognised link between complex Ca 2+ signals and the regulation of Ras.