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dc.contributor.authorWhiting, Jennifer L.
dc.contributor.authorNygren, Patrick J.
dc.contributor.authorTunquist, Brian J.
dc.contributor.authorLangeberg, Lorene K.
dc.contributor.authorSeternes, Ole Morten
dc.contributor.authorScott, John D.
dc.date.accessioned2022-04-19T08:26:18Z
dc.date.available2022-04-19T08:26:18Z
dc.date.issued2015-06-18
dc.description.abstractThe proximity of an enzyme to its substrate can influence rate and magnitude of catalysis. A-kinase anchoring protein 220 (AKAP220) is a multivalent anchoring protein that can sequester a variety of signal transduction enzymes. These include protein kinase A (PKA) and glycogen synthase kinase 3 (GSK3). Using a combination of molecular and cellular approaches we show that GSK3 phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3 and its substrate -catenin in membrane ruffles. Interestingly, GSK3 can be released from the multienzyme complex in response to PKA phosphorylation on serine 9, which suppresses GSK3 activity. The signaling scaffold may enhance this regulatory mechanism, as AKAP220 has the capacity to anchor two PKA holoenzymes. Site 1 on AKAP220 (residues 610– 623) preferentially interacts with RII, whereas site 2 (residues 1633–1646) exhibits a dual specificity for RI and RII. In vitro affinity measurements revealed that site 2 on AKAP220 binds RII with 10-fold higher affinity than site 1. Occupancy of both R subunit binding sites on AKAP220 could provide a mechanism to amplify local cAMP responses and enable cross-talk between PKA and GSK3.en_US
dc.identifier.citationWhiting, Nygren, Tunquist, Langeberg, Seternes om, Scott JD. Protein kinase A opposes the phosphorylation-dependent recruitment of glycogen synthase kinase 3β to A-kinase Anchoring Protein 220. Journal of Biological Chemistry. 2015;290(32):19445-19457en_US
dc.identifier.cristinIDFRIDAID 1278144
dc.identifier.doi10.1074/jbc.M115.654822
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttps://hdl.handle.net/10037/24798
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Biological Chemistry
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2015 he American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.titleProtein kinase A opposes the phosphorylation-dependent recruitment of glycogen synthase kinase 3β to A-kinase Anchoring Protein 220en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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