Identification of an IQGAP1/AKAP79 complex in beta-cells.
IQGAP1, is a recently discovered scaffold protein proposed to regulate membrane cytoskeleton events through protein-protein interactions with F-actin, E-cadherin, beta-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.
Nauert
J Brian
JB
Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health and Science University, L607 Portland, Oregon, USA.
Rigas
Johanna D
JD
Lester
Linda B
LB
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D046911:Macromolecular Substances; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D002147:Calmodulin; D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D020703:ras GTPase-Activating Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D002118:Calcium