Evidence map›Paper›PMID 25769305›Full record

ArticleMolecular pharmacology2015

Cyclic Adenosine 3',5'-Monophosphate Elevation and Biological Signaling through a Secretin Family Gs-Coupled G Protein-Coupled Receptor Are Restricted to a Single Adenylate Cyclase Isoform.

Andrew C Emery, Xiu-Huai Liu, Wenqin Xu, Maribeth V Eiden, Lee E Eiden

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022
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  5. Review
  6. What's New in Endocrinology: The Chromaffin Cell.Frontiers in endocrinology · 2018
    Review
  7. Article
  8. Review
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

5 authors at 1 institution in 1 country.

Andrew C EmerySections on Molecular Neuroscience (A.C.E., X.-H.L., L.E.E.) and Directed Gene Transfer (W.X., M.V.E.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland.ORCID http://orcid.org/0000-0002-6760-2570
Xiu-Huai LiuSections on Molecular Neuroscience (A.C.E., X.-H.L., L.E.E.) and Directed Gene Transfer (W.X., M.V.E.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland.
Wenqin XuSections on Molecular Neuroscience (A.C.E., X.-H.L., L.E.E.) and Directed Gene Transfer (W.X., M.V.E.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland.
Maribeth V EidenSections on Molecular Neuroscience (A.C.E., X.-H.L., L.E.E.) and Directed Gene Transfer (W.X., M.V.E.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland eidenl@mail.nih.gov eidenm@mail.nih.gov.
Lee E EidenSections on Molecular Neuroscience (A.C.E., X.-H.L., L.E.E.) and Directed Gene Transfer (W.X., M.V.E.), Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland eidenl@mail.nih.gov eidenm@mail.nih.gov.
National Institute of Mental Health · US

Funding

Chemical Coding Of NeurotransmissionZIAMH002386 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI EIDEN, LEE E. · 2009 to 2025
$25.6M
Viral And Cellular Factors Governing Efficient Gene DeliveryZIAMH002592 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI EIDEN, MARIBETH V. · 2009 to 2015
$7.9M
Intramural NIH HHS ZIA MH002386Intramural NIH HHS ZIA MH002592PHS HHS 1ZIAMH002386PHS HHS 1ZIAMH002592
6 · The paper itself

Abstract

PC12 cells express five adenylate cyclase (AC) isoforms, most abundantly AC6 and AC7. These two ACs were individually silenced using lentiviral short hairpin RNAs, which lead to a decrease (≥80%) of the protein product of each transcript. These stable PC12 sublines were then used to examine potential AC isoform preference for signaling through a family B G protein-coupled receptor (GPCR). Cells were challenged with the endogenous agonist of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1), pituitary adenylate cyclase-activating polypeptide (PACAP)-38, or the diterpene forskolin as an AC-proximal control. Intracellular cAMP levels were elevated by forskolin about equally in wild-type, AC6, and AC7 knockdown cells. The ability of PACAP-38 and forskolin to activate three cAMP sensors downstream of AC [protein kinase A (PKA), exchange protein activated by cAMP (Epac) 2/Rapgef4, and neuritogenic cAMP sensor (NCS)/Rapgef2] was examined by monitoring the phosphorylation status of their respective targets, cAMP response element-binding protein, p38, and extracellular signal-regulated kinase. Forskolin stimulation of each downstream target of cAMP was unaffected by knockdown of either AC6 or AC7. PACAP-38 activation of all downstream targets of cAMP was unaffected by AC7 knockdown, but abolished following AC6 knockdown. Membrane cholesterol depletion with methyl-β-cyclodextrin mimicked the effects of AC6 silencing on PACAP signaling, without attenuating forskolin signaling. These data suggest that vicinal constraint of the GPCR PAC1 and AC6 determines the exclusive requirement for this AC in PACAP signaling, but that the coupling of the cAMP sensors PKA, Epac2/Rapgef4, and NCS/Rapgef2, to their respective downstream signaling targets, determines how cAMP signaling is parcellated to physiologic responses, such as neuritogenesis, upon GPCR-Gs activation in neuroendocrine cells.

Indexed as

Adenylyl CyclasesAnimalsCell DifferentiationCholesterolColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinExtracellular Signal-Regulated MAP KinasesGTP-Binding Protein alpha Subunits, GsGuanine Nucleotide Exchange FactorsIsoenzymesp38 Mitogen-Activated Protein KinasesPC12 CellsPhosphorylationPituitary Adenylate Cyclase-Activating Polypeptideadenylyl cyclase 6Adenylyl CyclasesCholesterolColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinExtracellular Signal-Regulated MAP KinasesGTP-Binding Protein alpha Subunits, GsGuanine Nucleotide Exchange FactorsIsoenzymesp38 Mitogen-Activated Protein KinasesPituitary Adenylate Cyclase-Activating PolypeptideRapgef2 protein, ratRapgef4 protein, ratReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I

Identifiers

PMID25769305
PMCPMC4429715
OpenAlexW2166135916

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.