Figure 1. Models for MLCP reactivation.
(A) A simplistic model in which pCPI-17 is dephosphorylated only by other phosphatases (PPU) immediately after it dissociates from MLCP. The rate-limiting step for MLCP reactivation is the dissociation, whose rate is koff. (B) A more realistic scenario in which pCPI-17 freed by dissociation can rebind to free MLCP, and in which pCPI-17 is in an equilibrium with unphosphorylated CPI-17 that depends on the relative activities of the kinases (PKC) and phosphatases (PPU) involved. The rate of MLCP inactivation must necessarily be slower than that in (A). (C) Unfair competition. pCPI-17 is removed from MLCP by dephosphorylation as well as by dissociation. Free pCPI-17 and unphosphorylated CPI-17 are in an equilibrium determined by the relative activities of the kinases (PKC) and phosphatases (MLCP and PPU) involved. When the concentration of pCPI-17 is less than or equal to the concentration of MLCP, the very low Km ensures that almost all pCPI-17 dephosphorylation is accomplished by MLCP.