1. Greg M. Findlay is at the Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
2. Tony Pawson is at the Samuel Lunenfeld Research Institute and the Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
   e-mail: pawson@mshri.on.ca

Abstract

New work shows that activation of the Ras guanine nucleotide exchange factor SOS is dependent upon the membrane density of phosphatidylinositol-4,5-bisphosphate (PIP₂) and GTP-bound Ras. These signals synergize to release the autoinhibitory DH-PH domain, while the histone domain fine-tunes SOS activation in response to PIP₂.

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