Evidence map›Paper›PMID 34314739›Full record

ArticleMolecular and cellular endocrinology2021

IGFBP-1 hyperphosphorylation in response to nutrient deprivation is mediated by activation of protein kinase Cα (PKCα).

Allan W Chen, Kyle Biggar, Karen Nygard, Sahil Singal, Tiffany Zhao, Cun Li, Peter W Nathanielsz, Thomas Jansson, Madhulika B Gupta

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

Article in Molecular and cellular endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
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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

9 authors at 4 institutions in 2 countries.

Allan W ChenDepartment of Biochemistry, University of Western Ontario, London, ON, Canada.
Kyle BiggarInstitute of Biochemistry, Carleton University, Ottawa, ON, Canada.
Karen NygardBiotron Integrated Microscopy Facility, University of Western Ontario, London, ON, Canada.
Sahil SingalDepartment of Biochemistry, University of Western Ontario, London, ON, Canada.
Tiffany ZhaoDepartment of Biochemistry, University of Western Ontario, London, ON, Canada.
Cun LiUniversity of Wyoming, Laramie, WY, USA; Southwest National Primate Research Center, San Antonio, TX, USA.
Peter W NathanielszUniversity of Wyoming, Laramie, WY, USA; Southwest National Primate Research Center, San Antonio, TX, USA.
Thomas JanssonDepartment of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Madhulika B GuptaDepartment of Biochemistry, University of Western Ontario, London, ON, Canada; Department of Pediatrics, University of Western Ontario, London, ON, Canada; Children's Health Research Institute, London, ON, Canada. Electronic address: mbgupta@uwo.ca.
Western University · CAUniversity of Wyoming · USCarleton University · CAUniversity of Colorado Anschutz Medical Campus · US

Funding

The Southwest National Primate Research Center Supplement- Infrastructure improvements of ABSL2 holding areasP51OD011133 · OD · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI Larry S. Schlesinger · 2012 to 2026
$129.7M
PARTURITION AND FETAL PRIMATE HYPOTHALAMIC FUNCTIONP01HD021350 · NICHD · UNIVERSITY OF WYOMING · PI JANSSON, THOMAS · 1987 to 2018
$19.9M
Womb to Tomb: Developmental Programming and Aging Interactions in PrimatesU19AG057758 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI CLARKE, GEOFFREY DAVID, COX, LAURA A · 2018 to 2024
$13.2M
IGFBP-1 hyperphosphorylation in IUGR: Role of mTOR and CK2R03HD078313 · NICHD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GUPTA, MADHULIKA, JANSSON, THOMAS · 2014 to 2015
$147k
Regulation of IGFBP-1 Phosphorylation in Fetal DevelopmentR03HD093950 · NICHD · UNIVERSITY OF COLORADO DENVER · PI GUPTA, MADHULIKA, JANSSON, THOMAS · 2018 to 2019
$144k
NIA NIH HHS U19 AG057758NICHD NIH HHS P01 HD021350NICHD NIH HHS R03 HD078313NICHD NIH HHS R03 HD093950NIH HHS P51 OD011133
6 · The paper itself

Abstract

Fetal growth restriction (FGR) is associated with decreased nutrient availability and reduced insulin-line growth factor (IGF)-I bioavailability via increased IGF binding protein (IGFBP)-1 phosphorylation. While protein kinase C (PKC) is implicated in IGFBP-1 hyperphosphorylation in nutrient deprivation, the mechanisms remain unclear. We hypothesised that the interaction of PKCα with protein kinase CK2β and activation of PKCα under leucine deprivation (L0) mediate fetal hepatic IGFBP-1 hyperphosphorylation. Parallel Reaction Monitoring Mass Spectrometry (PRM-MS) followed by PKCα knockdown demonstrated the PKCα isoform interacts with IGFBP-1 and CK2β under L0. Pharmacological PKCα activation with phorbol 12-myristate 13-acetate (PMA) increased whereas inhibition with bisindolylmaleimide II (Bis II) decreased IGFBP-1 phosphorylation (Ser101/119/169, Ser98 + 101 and Ser169 + 174), respectively. Furthermore, PMA mimicked L0-induced PKCα translocation and IGFBP-1 expression. PKCα expression was increased in baboon fetal liver in FGR, providing biological relevance in vivo. In summary, we report a novel nutrient-sensitive mechanism for PKCα in mediating IGFBP-1 hyperphosphorylation in FGR.

Indexed as

AnimalsCasein Kinase IIFetal Growth RetardationGene Knockdown TechniquesHep G2 CellsHumansIndolesInsulin-Like Growth Factor Binding Protein 1LeucineLiverMaleimidesMass SpectrometryModels, BiologicalPapioPhosphorylationProtein Kinase C-alphabisindolylmaleimide IICasein Kinase IIIGFBP1 protein, humanIndolesInsulin-Like Growth Factor Binding Protein 1LeucineMaleimidesPRKCA protein, humanProtein Kinase C-alphaTetradecanoylphorbol AcetateBaboonFetal growth restrictionPlacental insufficiencyProtein interactionProtein kinase CK2

Identifiers

PMID34314739
PMCPMC8634829
OpenAlexW3183662744

What OpenQuestion holds

Textmetadata
LicenceTDM
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.