Abstract
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.
Copyright 2003 Wiley-Liss, Inc.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
A Kinase Anchor Proteins
-
Adaptor Proteins, Signal Transducing*
-
Animals
-
Calcium / metabolism
-
Calmodulin / metabolism
-
Carrier Proteins / metabolism*
-
Cattle
-
Cell Membrane / metabolism
-
Cells, Cultured
-
Cyclic AMP / metabolism
-
Cyclic AMP-Dependent Protein Kinases / metabolism
-
Humans
-
Islets of Langerhans / cytology
-
Islets of Langerhans / metabolism*
-
Macromolecular Substances
-
Protein Binding
-
Protein Structure, Tertiary
-
Rats
-
Recombinant Proteins / metabolism
-
Signal Transduction / physiology*
-
cdc42 GTP-Binding Protein / metabolism
-
rac GTP-Binding Proteins / metabolism
-
ras GTPase-Activating Proteins*
Substances
-
A Kinase Anchor Proteins
-
AKAP5 protein, human
-
Adaptor Proteins, Signal Transducing
-
Akap5 protein, rat
-
Calmodulin
-
Carrier Proteins
-
IQ motif containing GTPase activating protein 1
-
Macromolecular Substances
-
Recombinant Proteins
-
ras GTPase-Activating Proteins
-
Cyclic AMP
-
Cyclic AMP-Dependent Protein Kinases
-
cdc42 GTP-Binding Protein
-
rac GTP-Binding Proteins
-
Calcium