title: Membrane-dependent signal integration by the Ras activator Son of sevenless.
abstract: 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 (SOS(cat)) is up to 500-fold higher when Ras is on membranes compared to rates in solution, because the allosteric Ras site anchors SOS(cat) 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.
authors.affiliation: Department of Molecular and Cell Biology, and Howard Hughes Medical Institute, QB3 Institute, 176 Stanley Hall, University of California, Berkeley, California 94720, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Gureasko
authors.forename: William J
authors.initials: WJ
authors.lastname: Galush
authors.forename: Sean
authors.initials: S
authors.lastname: Boykevisch
authors.forename: Holger
authors.initials: H
authors.lastname: Sondermann
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
authors.forename: Jay T
authors.initials: JT
authors.lastname: Groves
authors.forename: John
authors.initials: J
authors.lastname: Kuriyan
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D020837:SOS1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D020837:SOS1 Protein; D018631:ras Proteins