Editors' ChoiceBiochemistry

Outliers Dominate Signaling at Cell Membrane

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Sci. Signal.  08 Jul 2014:
Vol. 7, Issue 333, pp. ec189
DOI: 10.1126/scisignal.2005656

SOS enzymes act at cell membranes to activate Ras, a regulatory protein often overactive in cancer cells. Iversen et al. devised a system where they could observe the activity of individual enzymes at work. The single SOS molecules occupied stable states that varied greatly in their catalytic activity. Regulation appeared to occur by altering the time spent in active states. The overall activity of SOS was determined by just a few molecules that achieved the highest catalytic activity. The methods described should allow further detailed kinetic analysis of this and other signaling events that occur at the cell membrane—properties that it is not possible to discern from bulk biochemical measurements.

L. Iversen, H.-L. Tu, W.-C. Lin, S. M. Christensen, S. M. Abel, J. Iwig, H.-J. Wu, J. Gureasko, C. Rhodes, R. S. Petit, S. D. Hansen, P. Thill, C.-H. Yu, D. Stamou, A. K. Chakraborty, J. Kuriyan, J. T. Groves, Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics. Science 344, 50–54 (2014). [Abstract] [Full Text]