Evidence map›Paper›PMID 24555506›Full record

ArticleThe Biochemical journal2014

The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s).

Moses Xie, Brigitte Blackman, Colleen Scheitrum, Delphine Mika, Elise Blanchard, Tao Lei, Marco Conti, Wito Richter

Open access · greenAbstract readComparative Study
In one paragraph

Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
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  8. Ablation of PDE4B protects from Pseudomonas aeruginosa-induced acute lung injury in mice by ameliorating the cytostorm and associated hypothermia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
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  13. Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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  20. Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4.Proceedings of the National Academy of Sciences of the United States of America · 2015
    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

8 authors at 1 institution in 1 country.

Moses Xie*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Brigitte Blackman*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Colleen Scheitrum*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Delphine Mika*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Elise Blanchard*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Tao Lei*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Marco Conti*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
Wito Richter*Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143, U.S.A.
University of California, San Francisco · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Hormonal Regulation of PhosphodiestrasesR01HL092788 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CONTI, MARCO · 2008 to 2012
$1.9M
Targeting compartmentalized phosphodiesterases to regulate CFTR functionR21HL107960 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RICHTER, WITO H · 2012 to 2013
$377k
NHLBI NIH HHS HL092788NHLBI NIH HHS HL107960NHLBI NIH HHS R01 HL092788NHLBI NIH HHS R21 HL107960NIDDK NIH HHS DK072517NIDDK NIH HHS P30 DK072517
6 · The paper itself

Abstract

PDE4s (type 4 cyclic nucleotide phosphodiesterases) are divided into long and short forms by the presence or absence of conserved N-terminal domains termed UCRs (upstream conserved regions). We have shown previously that PDE4D2, a short variant, is a monomer, whereas PDE4D3, a long variant, is a dimer. In the present study, we have determined the apparent molecular masses of various long and short PDE4 variants by size-exclusion chromatography and sucrose density-gradient centrifugation. Our results indicate that dimerization is a conserved property of all long PDE4 forms, whereas short forms are monomers. Dimerization is mediated by the UCR domains. Given their high sequence conservation, the UCR domains mediate not only homo-oligomerization, but also hetero-oligomerization of distinct PDE4 long forms as detected by co-immunoprecipitation assays and FRET microscopy. Endogenous PDE4 hetero-oligomers are, however, low in abundance compared with homo-dimers, revealing the presence of mechanisms that predispose PDE4s towards homo-oligomerization. Oligomerization is a prerequisite for the regulatory properties of the PDE4 long forms, such as their PKA (protein kinase A)-dependent activation, but is not necessary for PDE4 protein-protein interactions. As a result, individual PDE4 protomers may independently mediate protein-protein interactions, providing a mechanism whereby PDE4s contribute to the assembly of macromolecular signalling complexes.

Indexed as

Amino Acid SequenceAnimalsChlorocebus aethiopsConserved SequenceCOS CellsCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4CytosolDimerizationEnzyme ActivationHEK293 CellsHumansIsoenzymesLuminescent ProteinsMolecular WeightPhosphorylationCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4IsoenzymesLuminescent ProteinsRecombinant Fusion ProteinsRecombinant Proteins

Identifiers

PMID24555506
PMCPMC4315173
OpenAlexW2023810575

What OpenQuestion holds

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Registered trials

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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.