A-Kinase Anchoring Protein AKAP220 Binds to Glycogen Synthase Kinase-3β (GSK-3β) and Mediates Protein Kinase A-dependent Inhibition of GSK-3β

Glycogen synthase kinase-3 (GSK-3) is regulated by various extracellular ligands and phosphorylates many substrates, thereby regulating cellular functions. Using yeast two-hybrid screening, we found that GSK-3β binds to AKAP220, which is known to act as an A-kinase anchoring protein. GSK-3β formed a...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-10, Vol.277 (40), p.36955-36961
Main Authors: Tanji, Chie, Yamamoto, Hideki, Yorioka, Noriaki, Kohno, Nobuoki, Kikuchi, Kunimi, Kikuchi, Akira
Format: Article
Language:English
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Summary:Glycogen synthase kinase-3 (GSK-3) is regulated by various extracellular ligands and phosphorylates many substrates, thereby regulating cellular functions. Using yeast two-hybrid screening, we found that GSK-3β binds to AKAP220, which is known to act as an A-kinase anchoring protein. GSK-3β formed a complex with AKAP220 in intact cells at the endogenous level. Cyclic AMP-dependent protein kinase (PKA) and type 1 protein phosphatase (PP1) were also detected in this complex, suggesting that AKAP220, GSK-3β, PKA, and PP1 form a quaternary complex. It has been reported that PKA phosphorylates GSK-3β, thereby decreasing its activity. When COS cells were treated with dibutyryl cyclic AMP to activate PKA, the activity of GSK-3β bound to AKAP220 decreased more markedly than the total GSK-3β activity. Calyculin A, a protein phosphatase inhibitor, also inhibited the activity of GSK-3β bound to AKAP220 more strongly than the total GSK-3β activity. These results suggest that PKA and PP1 regulate the activity of GSK-3β efficiently by forming a complex with AKAP220.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M206210200