AbstractIQGAP1, is a recently discovered scaffold protein proposed to regulate membrane cytoskeleton events through protein–protein interactions with F‐actin, E‐cadherin, β‐catenin, and CLIP170. The binding of IQGAP1 to its partners is regulated by calcium/calmodulin (Ca++/CaM) and the small molecular weight guanine nucleotide triphosphatases (GTPases), Cdc42, and Rac1. Here we identify a novel IQGAP1 scaffolding function by isolating the cyclic AMP dependent kinase (PKA) with IQGAP1. IQGAP1 was co‐purified with PKA using 5′‐cyclic AMP (cAMP) affinity chromatography and PKA activity was co‐immunoprecipitated with IQGAP1 using an anti‐IQGAP1 antibody. The association of IQGAP1 with PKA was shown to occur through a direct interaction between A kinase anchoring protein 79 (AKAP79) and the carboxyl‐terminal domain of IQGAP1. This suggests that cAMP/PKA may be coupled with Ca++/CaM and GTPases through an IQGAP1/AKAP79 complex. J. Cell. Biochem. 90: 97–108, 2003. © 2003 Wiley‐Liss, Inc.