Figure 1. IQGAP1 scaffolds both the Ras‐ERK and PI3K‐Akt pathways.

The binding of all the components of the pathways to IQGAP1 facilitates sequential phosphorylation, leading to ERK or Akt activation. Pan et al (2017) reveal that an Akt target FOXO1 also binds to IQGAP1. The binding of phosphorylated FOXO1 induces conformation changes, which in turn promote dissociation of Ras‐ERK pathway components from IQGAP1 scaffold. Cellular concentration of IQGAP1 appears to modulate the pathway switch. At higher concentration, IQGAP1 largely scaffolds the PI3K‐Akt pathway, whereas at lower concentration, IQGAP1 scaffold is utilized for the Ras‐ERK pathway. CHD, calponin homology domain; CC, coiled‐coil; WW, WW domain; IQ, IQ domain; GRD, GTPase‐activating protein‐related domain; PI4K, phosphatidylinositol 4‐kinase.