History
IQGAP1 was discovered in 1994. Its name stems from the fact that its RasGAP-related domain (GRD) has sequence homology to the Sar1 GTPase. It was hypothesized that IQGAP1 would act as a GTPase activating protein (GAP) protein, promoting the switch of ras GTPases from the active GTP to GDP-bound forms. However, despite the homology of IQGAP’s GAP domain to sar1 and the fact that IQGAP1 binds Rho GTPases Rac1 and Cdc42, IQGAP does not actually have GAP function. Instead, it binds the active (GTP-bound) forms of RAC1 and CDC42 with higher affinity than GDP-bound forms, and stabilizes the active form in vivo.
IQGAP1 is now recognized as a protein scaffold that integrates signals regulating cell adhesion, actin cytoskeleton, the cell cycle, and other cellular functions. IQGAP is particularly interesting as a therapeutic target since it acts as a node for so many signaling pathways implicated in cancer progression.
Read more about this topic: IQGAP1
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