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GTPases (Ras, Rho, cdc42Hs, and rac) modulate various cellular functions such as cytoskeletal architecture, growth, motility, and gene expression. The activity of the GTP-binding proteins is regulated by factors that accelerate GTP-binding (GAPs) and proteins that enhance the rate of GTP hydrolysis (GTPases). IQGAP1 is Ras-GAP related protein that contains a WW domain that binds poly-proline regions, a calponin-homology domain (CHD), an IQ domain of unconventional myosins, and a C-terminal GAP-related domain (GRD). IQGAP1 co-immunoprecipitates with cdc42 and calmodulin, and colocalizes with cdc42Hs at the leading edges of the plasma membrane and at the cell-cell junctions. IQGAP1 may interact with both cadherins and catenins leading to dissociation of these proteins from sites of cell adhesion. Thus, IQGAP1 may be a Rac1 and Cdc42 effector that negatively regulates cadherin-mediated cell junctions.
