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Sci. Signal., 3 January 2012
Vol. 5, Issue 205, p. ra2
The model organism Dictyostelium moves toward higher concentrations of the chemoattractant cAMP (cyclic adenosine monophosphate), which activates a receptor that then stimulates effector proteins of the Ras family. Takeda et al. sought to understand how Dictyostelium adapts to rapid changes in chemoattractant by measuring the kinetics of Ras activation in cells exposed to cAMP. Mathematical modeling indicated that a signaling network in which the chemoattractant activates two components, which respectively activate and inhibit a third component, accurately described the data obtained from cAMP-stimulated cells. This type of network, called incoherent feedforward control, may be conserved in other chemotactic signaling networks.
Citation: K. Takeda, D. Shao, M. Adler, P. G. Charest, W. F. Loomis, H. Levine, A. Groisman, W.-J. Rappel, R. A. Firtel, Incoherent Feedforward Control Governs Adaptation of Activated Ras in a Eukaryotic Chemotaxis Pathway. Sci. Signal.5, ra2 (2012).
Chemoattractant stimulation of TORC2 is regulated by receptor/G protein-targeted inhibitory mechanisms that function upstream and independently of an essential GEF/Ras activation pathway in Dictyostelium.