Figure 4. Dynamic modeling of RAF, MEK and ERK after ligand binding.

In the initial state, RAF is clustered around the CM and MEK and ERK around the NM. When ligand binds the membrane receptor, RAF is phosphorylated. The negative chareges interact with the intracellular field resulting in rapid (<0.01 sec) movement of pRAF toward the NM. As it reaches the perinuclear region, pRAF encounters and phosphorylates several MEK proteins which, in turn, phosphorylate several ERK proteins. The rapid, direct movement of pRAF provides spatial and temporal information while the interactions with MEK and ERK amplify the signal at the NM. The pRAF is assumed to encounter a phosphorylase after about 30 seconds. The loss of negative charges causes RAF to return to it original isoelectric point with very rapid (<0.01 sec) return to the CM where it is again available for signal transduction.