Jodi Gureasko

TL;DR: It is found that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine in the activation loop, which suggests that the Kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation.

TL;DR: It is shown that SOS responds to the membrane density of Ras molecules, to their state of GTP loading and to the membranes concentration of phosphatidylinositol-4,5-bisphosphate (PIP2), and that the integration of these signals potentiates the release of autoinhibition.

TL;DR: Describing the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.

TL;DR: The results indicate that the histone domain and the DH-PH unit are conformationally coupled, and that the simultaneous engagement of the membrane by a PH domain PIP2-binding interaction and electrostatic interactions between a conserved positively charged patch on the hist onedomain and the negatively charged membrane coincides with a productive reorientation of SOS at the membrane and increased accessibility of both Ras binding sites on SOS.