Figure 8.

Model depicting the interaction between Ca²⁺/calmodulin and KSR1 in MAPK signaling. A, Ca²⁺/calmodulin binds constitutively to KSR1. Stimulation of EGFR induces both the activation of Ras at the plasma membrane and dissociation of Ca²⁺/calmodulin from KSR1. The latter enables KSR1 to translocate to the plasma membrane where it scaffolds Raf/MEK/ERK, enabling ERK activation. B, the calmodulin antagonist CGS9343B prevents the dissociation of Ca²⁺/calmodulin from KSR1. The Ca²⁺/calmodulin-KSR1 complex is unable to move to the plasma membrane, attenuating MAPK activation. Other proteins that bind KSR1 are not included for clarity. CaM, calmodulin; EGFR, EGF receptor; P, phosphate.