FIG. 12.

Model of IQGAP1 functioning as a scaffold in the MAP kinase pathway. (A) When the concentration of the scaffolding protein, IQGAP1, is too low, functional IQGAP1 complexes containing MEK and ERK are unable to form. (B) At the optimal scaffold concentration, the kinases are in an appropriate stoichiometric ratio with IQGAP1. Functional MAP kinase signaling complexes are formed. (C) When the concentration of IQGAP1 is excessive, many different IQGAP1 molecules harboring only one of the components of the cascade form complexes, which cannot function optimally. The binding site for ERK2 on IQGAP1 is the region containing the polyproline binding domain (WW) and that of MEK is the region spanning the calmodulin-binding motif (IQ). Raf binding to IQGAP1 has not been documented.