(A) RAS immobilized on microbeads is used to study the effects of GEFs and GAPs on RAS activation as measured by the recruitment of a labeled RAF1-RBD. (B) A positive feedback that recruits more GEF (RBD-RasGRF) to beads as more RAS is activated amplifies weak input signals under high GAP conditions. (C) The allosteric feedback whereby RAS:GTP binds to and activates SOS reduces overshoot in the output dynamics. Panels (A–C) are adapted from [52]. (D) Feedback regulation of SOS and NF1. Green arrow, activation; red blunt-end lines, inhibition.