IQGAP1, for IQ motif containing GTPase activating protein, is a Ras GAP-related, Actin-binding protein that interacts with the small GTPases Cdc42 and Rac1. The C-terminus of IQGAP1 is essential for interacting with Cdc42 and, in addition, IQGAP1 contains a WW domain and a predicted N-terminal coiled-coil region, which may be involved in IQGAP dimerization. Expression of IQGAP1 is highest in placenta, lung and kidney, where it co-localizes with Cdc42 to the cytoskeleton and assists with Cdc42 in mediating the regulation of cell proliferation, polarity and cell morphology. IQGAP1 regulates cadherin-mediated cell adhesion via binding to E-cadherin, b-catenin and a-catenin. This association induces the accumulation of these proteins at the site of cell-cell contact. IQGAP1 is negatively regulated by calmodulin, which binds to IQGAP1 in a calcium-dependent manner and disrupts IQGAP1 from associating with Cdc42.
