Evidence map›Paper›PMID 26088133›Full record

ArticleThe Journal of biological chemistry2015

Protein Kinase A Opposes the Phosphorylation-dependent Recruitment of Glycogen Synthase Kinase 3β to A-kinase Anchoring Protein 220.

Jennifer L Whiting, Patrick J Nygren, Brian J Tunquist, Lorene K Langeberg, Ole-Morten Seternes, John D Scott

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
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  9. Review
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  14. Article
  15. Review
  16. AKAP Signaling Islands: Venues for Precision Pharmacology.Trends in pharmacological sciences · 2020
    Review
  17. Article
  18. Prostaglandin EFrontiers in pharmacology · 2019
    Article
  19. Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Jennifer L WhitingFrom the Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195.
Patrick J NygrenFrom the Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195.
Brian J TunquistTranslational Oncology, Array BioPharma, Inc., Boulder, Colorado 80301, and.
Lorene K LangebergFrom the Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195.
Ole-Morten SeternesFrom the Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, Department of Pharmacy, University of Tromsø, The Arctic University of Norway, 9037 Tromsø, Norway.
John D ScottFrom the Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, scottjdw@uw.edu.
Array BioPharma (United States) · USUniversity of Washington · US

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Sakeneh Zraika · 1986 to 2026
$41.4M
Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
Local Signaling in Diabetic ComorbiditiesR01DK105542 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCOTT, JOHN D · 2015 to 2018
$1.4M
Howard Hughes Medical InstituteNIDDK NIH HHS DK054441NIDDK NIH HHS DK105542NIDDK NIH HHS P01 DK054441NIDDK NIH HHS P30 DK017047NIDDK NIH HHS R01 DK105542NIGMS NIH HHS T32 GM007750
6 · The paper itself

Abstract

The 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 3β (GSK3β). Using a combination of molecular and cellular approaches we show that GSK3β phosphorylation of Thr-1132 on AKAP220 initiates recruitment of this kinase into the enzyme scaffold. We also find that AKAP220 anchors GSK3β and its substrate β-catenin in membrane ruffles. Interestingly, GSK3β can be released from the multienzyme complex in response to PKA phosphorylation on serine 9, which suppresses GSK3β 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 GSK3β.

Indexed as

A Kinase Anchor ProteinsAmino Acid SequenceAnimalsBinding SitesCell LineCyclic AMP-Dependent Protein KinasesEpithelial CellsGene Expression RegulationGenetic EngineeringGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHEK293 CellsHoloenzymesHumansMiceMolecular Sequence DataA Kinase Anchor ProteinsCyclic AMP-Dependent Protein KinasesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseHoloenzymesProtein SubunitsRecombinant ProteinsA-kinase anchoring protein (AKAP)cyclic AMP (cAMP)glycogen synthase kinase 3 (GSK-3)protein complexprotein kinaseprotein kinase A (PKA)protein phosphorylationβ-catenin (B-catenin)

Identifiers

PMID26088133
PMCPMC4528109
OpenAlexW1738502657

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.