Article abstract

Nature Structural & Molecular Biology 15, 452 - 461 (2008)
Published online: 4 May 2008 | Corrected online: 15 May 2008 | doi:10.1038/nsmb.1418



There is an Erratum (June 2008) associated with this Article.

Membrane-dependent signal integration by the Ras activator Son of sevenless

Jodi Gureasko1,6, William J Galush2,6, Sean Boykevisch3, Holger Sondermann1,5, Dafna Bar-Sagi3, Jay T Groves2,4 & John Kuriyan1,4

The kinetics of Ras activation by Son of sevenless (SOS) changes profoundly when Ras is tethered to membranes, instead of being in solution. SOS has two binding sites for Ras, one of which is an allosteric site that is distal to the active site. The activity of the SOS catalytic unit (SOScat) is up to 500-fold higher when Ras is on membranes compared to rates in solution, because the allosteric Ras site anchors SOScat to the membrane. This effect is blocked by the N-terminal segment of SOS, which occludes the allosteric site. We show that SOS responds to the membrane density of Ras molecules, to their state of GTP loading and to the membrane concentration of phosphatidylinositol-4,5-bisphosphate (PIP2), and that the integration of these signals potentiates the release of autoinhibition.

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  1. Department of Molecular and Cell Biology, Department of Chemistry, and Howard Hughes Medical Institute, QB3 Institute, 176 Stanley Hall, University of California, Berkeley, California 94720, USA.
  2. Department of Chemistry, University of California, Berkeley, California 94720, USA.
  3. Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA.
  4. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
  5. Present address: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
  6. These authors contributed equally to this work.

Correspondence to: John Kuriyan1,4 e-mail: kuriyan@berkeley.edu

Correspondence to: Jay T Groves2,4 e-mail: jtgroves@lbl.gov

Correspondence to: Dafna Bar-Sagi3 e-mail: dafna.bar-sagi@nyumc.org

* In the version of this article initially published, the concentration units reported in Figure 7b,c should be nM, not nm. The green data series in Figure 7b should be labeled "SOScat". In addition, on page 452 of the article, the affiliation address for William J. Galush and Jay T. Groves was incorrect. Their correct address is Department of Chemistry, University of California, Berkeley, California 94720, USA. Finally, the last sentence of the Acknowledgments listed incorrect funding information. The last sentence should read, "J.T.G. and W.J.G. are supported by Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences of the US Department of Energy under Contract No. DE_AC03-76SF00098, and D.B.-S. by NIH GM078266." These errors have been corrected in the HTML and PDF versions of the article.

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