Figure 2.

Ras dynamics on the membrane. Inactive Ras diffuses more freely than active Ras. Lateral segregation and stochastic clustering of Ras isoforms appears to be predominantly mediated by HVR interactions with membrane lipids. In living cells, diffusion can be somewhat hindered by the subcortical actin meshwork (cross hatched). Current data suggest that transient immobilization of active Ras occurs after engagement of binding partners, such as RAF effectors (domains in yellow to orange). Both increased molecular mass and enhanced trapping in the actin meshwork contribute to hindered diffusion. The minimal core of these immobile nanoclusters appears to be the dimers of Ras bound to dimers of RAF, with RAF proteins actually ‘scaffolding’ the Ras nanoclusters by enhancing trapping events. RBD—Ras binding domain, CRD—cysteine rich domain, KD—kinase domain.