Evidence map›Paper›PMID 9736716›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1998

Blocking ligand occupancy of the alphaVbeta3 integrin inhibits insulin-like growth factor I signaling in vascular smooth muscle cells.

B Zheng, D R Clemmons

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 143 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Integrin signaling in atherosclerosis.Cellular and molecular life sciences : CMLS · 2017
    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

2 authors at 1 institution in 2 countries.

B ZhengDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
D R Clemmons
University of North Carolina at Chapel Hill · US

Funding

MECHANISMS BY WHICH IGF-I STIMULATES SMOOTH MUSCLE CELLSR01HL056850 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CLEMMONS, DAVID ROBERT · 1996 to 2007
$2.5M
NHLBI NIH HHS HL-56850NHLBI NIH HHS R01 HL056850
6 · The paper itself

Abstract

Blocking alphaVbeta3 integrin occupancy results in attenuation of the cellular migration response to insulin-like growth factor I (IGF-I). To determine whether integrin antagonists alter other IGF-I-stimulated biologic actions, quiescent smooth muscle cells (SMCs) were exposed to echistatin and their ability to respond to IGF-I was determined. Echistatin (10(-7) M) inhibited IGF-I-stimulated DNA synthesis by 80%, and the protein synthesis response also was inhibited. Therefore blocking occupancy of alphaVbeta3 inhibited multiple target cell actions of IGF-I. To determine whether blocking alphaVbeta3 occupancy could alter IGF-I receptor-mediated signal transduction, the ability of IGF-I to stimulate phosphorylation of insulin receptor substrate-1 (IRS-1) was analyzed. A 10-min exposure to 100 ng/ml of IGF-I resulted in a substantial increase in phosphorylated IRS-1, and echistatin (10(-7) M) blocked the IGF-I-induced IRS-1 phosphorylation response. Echistatin also attenuated downstream signaling because the capacity of the p85 subunit of phosphatidylinositol-3 kinase (PI-3 kinase) to bind to IRS-1 was blocked. In contrast, exposure of SMCs to vitronectin (1.0 micrograms/cm2) or thrombospondin (0.25 micrograms/cm2), two known ligands for alphaVbeta3, resulted in enhancement of the IGF-I-stimulated IRS-1 response. To determine whether these effects were caused by alterations in receptor kinase activity, the IGF-I receptor was immunoprecipitated and then analyzed for phosphotyrosine. Echistatin (10(-7) M) significantly reduced IGF-I-stimulated tyrosine phosphorylation of the IGF-I receptor beta subunit. We conclude that occupancy of the alphaVbeta3 integrin is necessary for IGF-I to fully activate the kinase activity of the IGF-I receptor and phosphorylate IRS-1. Activation of the alphaVbeta3 receptor results in an interaction with the IGF-I signal transduction pathway, which modulates SMCs responsiveness to IGF-I.

Indexed as

LigandsAnimalsBinding SitesCell MovementExtracellular Matrix ProteinsInsulin-Like Growth Factor IInsulin Receptor Substrate ProteinsIntercellular Signaling Peptides and ProteinsMuscle, Smooth, VascularNucleic Acid Synthesis InhibitorsPeptidesPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotyrosinePlatelet-Derived Growth FactorechistatinExtracellular Matrix ProteinsInsulin-Like Growth Factor IInsulin Receptor Substrate ProteinsIntercellular Signaling Peptides and ProteinsLigandsNucleic Acid Synthesis InhibitorsPeptidesPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphotyrosinePlatelet-Derived Growth FactorReceptors, VitronectinThrombospondinsThymidineVitronectin

Identifiers

PMID9736716
PMCPMC21622
OpenAlexW2083434885

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.